Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors
Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify geneti...
Ausführliche Beschreibung
Autor*in: |
Rashid, Khalid [verfasserIn] |
---|
Format: |
E-Artikel |
---|---|
Sprache: |
Englisch |
Erschienen: |
2018transfer abstract |
---|
Umfang: |
15 |
---|
Übergeordnetes Werk: |
Enthalten in: Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance - Yang, Zehui ELSEVIER, 2015transfer abstract, Amsterdam [u.a.] |
---|---|
Übergeordnetes Werk: |
volume:1861 ; year:2018 ; number:12 ; pages:1119-1133 ; extent:15 |
Links: |
---|
DOI / URN: |
10.1016/j.bbagrm.2018.10.018 |
---|
Katalog-ID: |
ELV045002681 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | ELV045002681 | ||
003 | DE-627 | ||
005 | 20230626010211.0 | ||
007 | cr uuu---uuuuu | ||
008 | 190205s2018 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.bbagrm.2018.10.018 |2 doi | |
028 | 5 | 2 | |a GBV00000000000433.pica |
035 | |a (DE-627)ELV045002681 | ||
035 | |a (ELSEVIER)S1874-9399(18)30365-1 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
082 | 0 | 4 | |a 620 |q VZ |
082 | 0 | 4 | |a 690 |q VZ |
084 | |a 50.92 |2 bkl | ||
100 | 1 | |a Rashid, Khalid |e verfasserin |4 aut | |
245 | 1 | 0 | |a Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
264 | 1 | |c 2018transfer abstract | |
300 | |a 15 | ||
336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
337 | |a nicht spezifiziert |b z |2 rdamedia | ||
338 | |a nicht spezifiziert |b zu |2 rdacarrier | ||
520 | |a Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. | ||
520 | |a Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. | ||
700 | 1 | |a Geissl, Lea |4 oth | |
700 | 1 | |a Wolf, Anne |4 oth | |
700 | 1 | |a Karlstetter, Marcus |4 oth | |
700 | 1 | |a Langmann, Thomas |4 oth | |
773 | 0 | 8 | |i Enthalten in |n Elsevier |a Yang, Zehui ELSEVIER |t Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |d 2015transfer abstract |g Amsterdam [u.a.] |w (DE-627)ELV01314085X |
773 | 1 | 8 | |g volume:1861 |g year:2018 |g number:12 |g pages:1119-1133 |g extent:15 |
856 | 4 | 0 | |u https://doi.org/10.1016/j.bbagrm.2018.10.018 |3 Volltext |
912 | |a GBV_USEFLAG_U | ||
912 | |a GBV_ELV | ||
912 | |a SYSFLAG_U | ||
912 | |a GBV_ILN_40 | ||
936 | b | k | |a 50.92 |j Meerestechnik |q VZ |
951 | |a AR | ||
952 | |d 1861 |j 2018 |e 12 |h 1119-1133 |g 15 |
author_variant |
k r kr |
---|---|
matchkey_str |
rashidkhalidgeisslleawolfannekarlstetter:2018----:rncitoargltootasoaopoen8dtpimcolae |
hierarchy_sort_str |
2018transfer abstract |
bklnumber |
50.92 |
publishDate |
2018 |
allfields |
10.1016/j.bbagrm.2018.10.018 doi GBV00000000000433.pica (DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 DE-627 ger DE-627 rakwb eng 620 VZ 690 VZ 50.92 bkl Rashid, Khalid verfasserin aut Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors 2018transfer abstract 15 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Geissl, Lea oth Wolf, Anne oth Karlstetter, Marcus oth Langmann, Thomas oth Enthalten in Elsevier Yang, Zehui ELSEVIER Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance 2015transfer abstract Amsterdam [u.a.] (DE-627)ELV01314085X volume:1861 year:2018 number:12 pages:1119-1133 extent:15 https://doi.org/10.1016/j.bbagrm.2018.10.018 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 50.92 Meerestechnik VZ AR 1861 2018 12 1119-1133 15 |
spelling |
10.1016/j.bbagrm.2018.10.018 doi GBV00000000000433.pica (DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 DE-627 ger DE-627 rakwb eng 620 VZ 690 VZ 50.92 bkl Rashid, Khalid verfasserin aut Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors 2018transfer abstract 15 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Geissl, Lea oth Wolf, Anne oth Karlstetter, Marcus oth Langmann, Thomas oth Enthalten in Elsevier Yang, Zehui ELSEVIER Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance 2015transfer abstract Amsterdam [u.a.] (DE-627)ELV01314085X volume:1861 year:2018 number:12 pages:1119-1133 extent:15 https://doi.org/10.1016/j.bbagrm.2018.10.018 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 50.92 Meerestechnik VZ AR 1861 2018 12 1119-1133 15 |
allfields_unstemmed |
10.1016/j.bbagrm.2018.10.018 doi GBV00000000000433.pica (DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 DE-627 ger DE-627 rakwb eng 620 VZ 690 VZ 50.92 bkl Rashid, Khalid verfasserin aut Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors 2018transfer abstract 15 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Geissl, Lea oth Wolf, Anne oth Karlstetter, Marcus oth Langmann, Thomas oth Enthalten in Elsevier Yang, Zehui ELSEVIER Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance 2015transfer abstract Amsterdam [u.a.] (DE-627)ELV01314085X volume:1861 year:2018 number:12 pages:1119-1133 extent:15 https://doi.org/10.1016/j.bbagrm.2018.10.018 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 50.92 Meerestechnik VZ AR 1861 2018 12 1119-1133 15 |
allfieldsGer |
10.1016/j.bbagrm.2018.10.018 doi GBV00000000000433.pica (DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 DE-627 ger DE-627 rakwb eng 620 VZ 690 VZ 50.92 bkl Rashid, Khalid verfasserin aut Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors 2018transfer abstract 15 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Geissl, Lea oth Wolf, Anne oth Karlstetter, Marcus oth Langmann, Thomas oth Enthalten in Elsevier Yang, Zehui ELSEVIER Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance 2015transfer abstract Amsterdam [u.a.] (DE-627)ELV01314085X volume:1861 year:2018 number:12 pages:1119-1133 extent:15 https://doi.org/10.1016/j.bbagrm.2018.10.018 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 50.92 Meerestechnik VZ AR 1861 2018 12 1119-1133 15 |
allfieldsSound |
10.1016/j.bbagrm.2018.10.018 doi GBV00000000000433.pica (DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 DE-627 ger DE-627 rakwb eng 620 VZ 690 VZ 50.92 bkl Rashid, Khalid verfasserin aut Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors 2018transfer abstract 15 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. Geissl, Lea oth Wolf, Anne oth Karlstetter, Marcus oth Langmann, Thomas oth Enthalten in Elsevier Yang, Zehui ELSEVIER Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance 2015transfer abstract Amsterdam [u.a.] (DE-627)ELV01314085X volume:1861 year:2018 number:12 pages:1119-1133 extent:15 https://doi.org/10.1016/j.bbagrm.2018.10.018 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 50.92 Meerestechnik VZ AR 1861 2018 12 1119-1133 15 |
language |
English |
source |
Enthalten in Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance Amsterdam [u.a.] volume:1861 year:2018 number:12 pages:1119-1133 extent:15 |
sourceStr |
Enthalten in Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance Amsterdam [u.a.] volume:1861 year:2018 number:12 pages:1119-1133 extent:15 |
format_phy_str_mv |
Article |
bklname |
Meerestechnik |
institution |
findex.gbv.de |
dewey-raw |
620 |
isfreeaccess_bool |
false |
container_title |
Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |
authorswithroles_txt_mv |
Rashid, Khalid @@aut@@ Geissl, Lea @@oth@@ Wolf, Anne @@oth@@ Karlstetter, Marcus @@oth@@ Langmann, Thomas @@oth@@ |
publishDateDaySort_date |
2018-01-01T00:00:00Z |
hierarchy_top_id |
ELV01314085X |
dewey-sort |
3620 |
id |
ELV045002681 |
language_de |
englisch |
fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV045002681</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626010211.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">190205s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.bbagrm.2018.10.018</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000433.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV045002681</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S1874-9399(18)30365-1</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">620</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">690</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">50.92</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Rashid, Khalid</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">15</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Geissl, Lea</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wolf, Anne</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Karlstetter, Marcus</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Langmann, Thomas</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Yang, Zehui ELSEVIER</subfield><subfield code="t">Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance</subfield><subfield code="d">2015transfer abstract</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV01314085X</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:1861</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:12</subfield><subfield code="g">pages:1119-1133</subfield><subfield code="g">extent:15</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.bbagrm.2018.10.018</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.92</subfield><subfield code="j">Meerestechnik</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">1861</subfield><subfield code="j">2018</subfield><subfield code="e">12</subfield><subfield code="h">1119-1133</subfield><subfield code="g">15</subfield></datafield></record></collection>
|
author |
Rashid, Khalid |
spellingShingle |
Rashid, Khalid ddc 620 ddc 690 bkl 50.92 Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
authorStr |
Rashid, Khalid |
ppnlink_with_tag_str_mv |
@@773@@(DE-627)ELV01314085X |
format |
electronic Article |
dewey-ones |
620 - Engineering & allied operations 690 - Buildings |
delete_txt_mv |
keep |
author_role |
aut |
collection |
elsevier |
remote_str |
true |
illustrated |
Not Illustrated |
topic_title |
620 VZ 690 VZ 50.92 bkl Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
topic |
ddc 620 ddc 690 bkl 50.92 |
topic_unstemmed |
ddc 620 ddc 690 bkl 50.92 |
topic_browse |
ddc 620 ddc 690 bkl 50.92 |
format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
format_main_str_mv |
Text Zeitschrift/Artikel |
carriertype_str_mv |
zu |
author2_variant |
l g lg a w aw m k mk t l tl |
hierarchy_parent_title |
Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |
hierarchy_parent_id |
ELV01314085X |
dewey-tens |
620 - Engineering 690 - Building & construction |
hierarchy_top_title |
Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |
isfreeaccess_txt |
false |
familylinks_str_mv |
(DE-627)ELV01314085X |
title |
Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
ctrlnum |
(DE-627)ELV045002681 (ELSEVIER)S1874-9399(18)30365-1 |
title_full |
Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
author_sort |
Rashid, Khalid |
journal |
Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |
journalStr |
Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance |
lang_code |
eng |
isOA_bool |
false |
dewey-hundreds |
600 - Technology |
recordtype |
marc |
publishDateSort |
2018 |
contenttype_str_mv |
zzz |
container_start_page |
1119 |
author_browse |
Rashid, Khalid |
container_volume |
1861 |
physical |
15 |
class |
620 VZ 690 VZ 50.92 bkl |
format_se |
Elektronische Aufsätze |
author-letter |
Rashid, Khalid |
doi_str_mv |
10.1016/j.bbagrm.2018.10.018 |
dewey-full |
620 690 |
title_sort |
transcriptional regulation of translocator protein (18 kda) (tspo) in microglia requires pu.1, ap1 and sp factors |
title_auth |
Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
abstract |
Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. |
abstractGer |
Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. |
abstract_unstemmed |
Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia. |
collection_details |
GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_40 |
container_issue |
12 |
title_short |
Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors |
url |
https://doi.org/10.1016/j.bbagrm.2018.10.018 |
remote_bool |
true |
author2 |
Geissl, Lea Wolf, Anne Karlstetter, Marcus Langmann, Thomas |
author2Str |
Geissl, Lea Wolf, Anne Karlstetter, Marcus Langmann, Thomas |
ppnlink |
ELV01314085X |
mediatype_str_mv |
z |
isOA_txt |
false |
hochschulschrift_bool |
false |
author2_role |
oth oth oth oth |
doi_str |
10.1016/j.bbagrm.2018.10.018 |
up_date |
2024-07-06T22:58:45.575Z |
_version_ |
1803872345077579776 |
fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV045002681</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230626010211.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">190205s2018 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.bbagrm.2018.10.018</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">GBV00000000000433.pica</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV045002681</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S1874-9399(18)30365-1</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">620</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">690</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">50.92</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Rashid, Khalid</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Transcriptional regulation of Translocator protein (18 kDa) (TSPO) in microglia requires Pu.1, Ap1 and Sp factors</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2018transfer abstract</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">15</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">z</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zu</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Mitochondrial Translocator protein (18 kDa) (TSPO) is strongly expressed in reactive microglia and serves as a therapeutic target for alleviation of neuronal degeneration. However, little is known about TSPO's transcriptional regulation in microglia. The aim of this study was to identify genetic elements and transcription factors required for basal and inducible TSPO expression in microglia. Murine Tspo promoter was cloned into the pGL4.10 luciferase vector and functionally characterized in BV-2 cells. Deletion mutagenesis indicated that −845 bases upstream were sufficient to reconstitute near maximal promoter activity in BV-2. Deletion of −593 to −520 sequences, which harbour an Ap1, Ets.2 and Nkx3.1 site which also serves as a non-canonical binding site for Sp1-family transcription factors, led to a dramatic decrease in both basal and LPS induced promoter activity. Further deletion of −168 to −39 sequences, which contains four GC boxes, also led to a significant decrease in promoter activity. Targeted mutations of Ap1, Ets.2, Nkx3.1/Sp1/3/4 and the GC boxes led to significant decreases in promoter activity. ChIP-qPCR revealed that Pu.1, Ap1, Stat3, Sp1, Sp3 and Sp4 bind to the endogenous Tspo promoter. Notably, binding of these factors, with the exception of Stat3, was significantly enhanced upon LPS treatment. RNAi silencing of Pu.1, cJun, cFos, Sp1, Sp3, Sp4 and Stat3 strongly lowered Tspo promoter activity while Ap1 silencing inhibited LPS induced increase in Tspo protein levels. These findings demonstrate that consensus binding sequences for Ap1, Ets.2, distal as well as proximal Sp1/3/4 sites regulate basal and LPS induced Tspo promoter activity in microglia.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Geissl, Lea</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wolf, Anne</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Karlstetter, Marcus</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Langmann, Thomas</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Yang, Zehui ELSEVIER</subfield><subfield code="t">Homogeneous coating of ionomer on electrocatalyst assisted by polybenzimidazole as an adhesive layer and its effect on fuel cell performance</subfield><subfield code="d">2015transfer abstract</subfield><subfield code="g">Amsterdam [u.a.]</subfield><subfield code="w">(DE-627)ELV01314085X</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:1861</subfield><subfield code="g">year:2018</subfield><subfield code="g">number:12</subfield><subfield code="g">pages:1119-1133</subfield><subfield code="g">extent:15</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.bbagrm.2018.10.018</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">50.92</subfield><subfield code="j">Meerestechnik</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">1861</subfield><subfield code="j">2018</subfield><subfield code="e">12</subfield><subfield code="h">1119-1133</subfield><subfield code="g">15</subfield></datafield></record></collection>
|
score |
7.400386 |