Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for t...
Ausführliche Beschreibung
Autor*in: |
Paolo Convertini [verfasserIn] Simona Todisco [verfasserIn] Francesco De Santis [verfasserIn] Ilaria Pappalardo [verfasserIn] Dominga Iacobazzi [verfasserIn] Maria Antonietta Castiglione Morelli [verfasserIn] Yvonne N. Fondufe-Mittendorf [verfasserIn] Giuseppe Martelli [verfasserIn] Ferdinando Palmieri [verfasserIn] Vittoria Infantino [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Übergeordnetes Werk: |
In: International Journal of Molecular Sciences - MDPI AG, 2003, 20(2019), 8, p 1888 |
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Übergeordnetes Werk: |
volume:20 ; year:2019 ; number:8, p 1888 |
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DOI / URN: |
10.3390/ijms20081888 |
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Katalog-ID: |
DOAJ008513619 |
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520 | |a Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). | ||
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10.3390/ijms20081888 doi (DE-627)DOAJ008513619 (DE-599)DOAJ4b3f28893f304cb6b10b8f919424921c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Paolo Convertini verfasserin aut Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). SLC25A13 AGC2 gene expression transcriptional regulation FOXA2 USF1 Biology (General) Chemistry Simona Todisco verfasserin aut Francesco De Santis verfasserin aut Ilaria Pappalardo verfasserin aut Dominga Iacobazzi verfasserin aut Maria Antonietta Castiglione Morelli verfasserin aut Yvonne N. Fondufe-Mittendorf verfasserin aut Giuseppe Martelli verfasserin aut Ferdinando Palmieri verfasserin aut Vittoria Infantino verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 20(2019), 8, p 1888 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:20 year:2019 number:8, p 1888 https://doi.org/10.3390/ijms20081888 kostenfrei https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c kostenfrei https://www.mdpi.com/1422-0067/20/8/1888 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 8, p 1888 |
spelling |
10.3390/ijms20081888 doi (DE-627)DOAJ008513619 (DE-599)DOAJ4b3f28893f304cb6b10b8f919424921c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Paolo Convertini verfasserin aut Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). SLC25A13 AGC2 gene expression transcriptional regulation FOXA2 USF1 Biology (General) Chemistry Simona Todisco verfasserin aut Francesco De Santis verfasserin aut Ilaria Pappalardo verfasserin aut Dominga Iacobazzi verfasserin aut Maria Antonietta Castiglione Morelli verfasserin aut Yvonne N. Fondufe-Mittendorf verfasserin aut Giuseppe Martelli verfasserin aut Ferdinando Palmieri verfasserin aut Vittoria Infantino verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 20(2019), 8, p 1888 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:20 year:2019 number:8, p 1888 https://doi.org/10.3390/ijms20081888 kostenfrei https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c kostenfrei https://www.mdpi.com/1422-0067/20/8/1888 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 8, p 1888 |
allfields_unstemmed |
10.3390/ijms20081888 doi (DE-627)DOAJ008513619 (DE-599)DOAJ4b3f28893f304cb6b10b8f919424921c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Paolo Convertini verfasserin aut Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). SLC25A13 AGC2 gene expression transcriptional regulation FOXA2 USF1 Biology (General) Chemistry Simona Todisco verfasserin aut Francesco De Santis verfasserin aut Ilaria Pappalardo verfasserin aut Dominga Iacobazzi verfasserin aut Maria Antonietta Castiglione Morelli verfasserin aut Yvonne N. Fondufe-Mittendorf verfasserin aut Giuseppe Martelli verfasserin aut Ferdinando Palmieri verfasserin aut Vittoria Infantino verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 20(2019), 8, p 1888 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:20 year:2019 number:8, p 1888 https://doi.org/10.3390/ijms20081888 kostenfrei https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c kostenfrei https://www.mdpi.com/1422-0067/20/8/1888 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 8, p 1888 |
allfieldsGer |
10.3390/ijms20081888 doi (DE-627)DOAJ008513619 (DE-599)DOAJ4b3f28893f304cb6b10b8f919424921c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Paolo Convertini verfasserin aut Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). SLC25A13 AGC2 gene expression transcriptional regulation FOXA2 USF1 Biology (General) Chemistry Simona Todisco verfasserin aut Francesco De Santis verfasserin aut Ilaria Pappalardo verfasserin aut Dominga Iacobazzi verfasserin aut Maria Antonietta Castiglione Morelli verfasserin aut Yvonne N. Fondufe-Mittendorf verfasserin aut Giuseppe Martelli verfasserin aut Ferdinando Palmieri verfasserin aut Vittoria Infantino verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 20(2019), 8, p 1888 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:20 year:2019 number:8, p 1888 https://doi.org/10.3390/ijms20081888 kostenfrei https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c kostenfrei https://www.mdpi.com/1422-0067/20/8/1888 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 8, p 1888 |
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10.3390/ijms20081888 doi (DE-627)DOAJ008513619 (DE-599)DOAJ4b3f28893f304cb6b10b8f919424921c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Paolo Convertini verfasserin aut Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). SLC25A13 AGC2 gene expression transcriptional regulation FOXA2 USF1 Biology (General) Chemistry Simona Todisco verfasserin aut Francesco De Santis verfasserin aut Ilaria Pappalardo verfasserin aut Dominga Iacobazzi verfasserin aut Maria Antonietta Castiglione Morelli verfasserin aut Yvonne N. Fondufe-Mittendorf verfasserin aut Giuseppe Martelli verfasserin aut Ferdinando Palmieri verfasserin aut Vittoria Infantino verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 20(2019), 8, p 1888 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:20 year:2019 number:8, p 1888 https://doi.org/10.3390/ijms20081888 kostenfrei https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c kostenfrei https://www.mdpi.com/1422-0067/20/8/1888 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 8, p 1888 |
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transcriptional regulation factors of the human mitochondrial aspartate/glutamate carrier gene, isoform 2 (<i<slc25a13</i<): usf1 as basal factor and foxa2 as activator in liver cells |
callnumber |
QH301-705.5 |
title_auth |
Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells |
abstract |
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). |
abstractGer |
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). |
abstract_unstemmed |
Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human <i<SLC25A13</i< gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (−442 bp/−19 bp), as well as an enhancer region (−968 bp/−768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for <i<SLC25A13</i< transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring <i<SLC25A13</i< gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for <i<SLC25A13</i< high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC). |
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container_issue |
8, p 1888 |
title_short |
Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (<i<SLC25A13</i<): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells |
url |
https://doi.org/10.3390/ijms20081888 https://doaj.org/article/4b3f28893f304cb6b10b8f919424921c https://www.mdpi.com/1422-0067/20/8/1888 https://doaj.org/toc/1422-0067 |
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author2 |
Simona Todisco Francesco De Santis Ilaria Pappalardo Dominga Iacobazzi Maria Antonietta Castiglione Morelli Yvonne N. Fondufe-Mittendorf Giuseppe Martelli Ferdinando Palmieri Vittoria Infantino |
author2Str |
Simona Todisco Francesco De Santis Ilaria Pappalardo Dominga Iacobazzi Maria Antonietta Castiglione Morelli Yvonne N. Fondufe-Mittendorf Giuseppe Martelli Ferdinando Palmieri Vittoria Infantino |
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316340715 |
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QH - Natural History and Biology |
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doi_str |
10.3390/ijms20081888 |
callnumber-a |
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up_date |
2024-07-03T18:26:28.350Z |
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