Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications

Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show t...
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Autor*in:	Antonietta Coppola [verfasserIn] Antonio Romito [verfasserIn] Christelle Borel [verfasserIn] Corinne Gehrig [verfasserIn] Maryline Gagnebin [verfasserIn] Emilie Falconnet [verfasserIn] Antonella Izzo [verfasserIn] Lucia Altucci [verfasserIn] Sandro Banfi [verfasserIn] Stylianos E. Antonarakis [verfasserIn] Gabriella Minchiotti [verfasserIn] Gilda Cobellis [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Übergeordnetes Werk:	In: Stem Cell Research - Elsevier, 2015, 12(2014), 2, Seite 323-337
Übergeordnetes Werk:	volume:12 ; year:2014 ; number:2 ; pages:323-337

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1016/j.scr.2013.11.008

Katalog-ID:	DOAJ03348662X

Internformat


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allfields	10.1016/j.scr.2013.11.008 doi (DE-627)DOAJ03348662X (DE-599)DOAJ9afed9bd1b1d496fab11a25aa8ee20b2 DE-627 ger DE-627 rakwb eng QH301-705.5 Antonietta Coppola verfasserin aut Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Biology (General) Antonio Romito verfasserin aut Christelle Borel verfasserin aut Corinne Gehrig verfasserin aut Maryline Gagnebin verfasserin aut Emilie Falconnet verfasserin aut Antonella Izzo verfasserin aut Lucia Altucci verfasserin aut Sandro Banfi verfasserin aut Stylianos E. Antonarakis verfasserin aut Gabriella Minchiotti verfasserin aut Gilda Cobellis verfasserin aut In Stem Cell Research Elsevier, 2015 12(2014), 2, Seite 323-337 (DE-627)548125856 (DE-600)2393143-7 18767753 nnns volume:12 year:2014 number:2 pages:323-337 https://doi.org/10.1016/j.scr.2013.11.008 kostenfrei https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 kostenfrei http://www.sciencedirect.com/science/article/pii/S1873506113001700 kostenfrei https://doaj.org/toc/1873-5061 Journal toc kostenfrei https://doaj.org/toc/1876-7753 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_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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2014 2 323-337
spelling	10.1016/j.scr.2013.11.008 doi (DE-627)DOAJ03348662X (DE-599)DOAJ9afed9bd1b1d496fab11a25aa8ee20b2 DE-627 ger DE-627 rakwb eng QH301-705.5 Antonietta Coppola verfasserin aut Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Biology (General) Antonio Romito verfasserin aut Christelle Borel verfasserin aut Corinne Gehrig verfasserin aut Maryline Gagnebin verfasserin aut Emilie Falconnet verfasserin aut Antonella Izzo verfasserin aut Lucia Altucci verfasserin aut Sandro Banfi verfasserin aut Stylianos E. Antonarakis verfasserin aut Gabriella Minchiotti verfasserin aut Gilda Cobellis verfasserin aut In Stem Cell Research Elsevier, 2015 12(2014), 2, Seite 323-337 (DE-627)548125856 (DE-600)2393143-7 18767753 nnns volume:12 year:2014 number:2 pages:323-337 https://doi.org/10.1016/j.scr.2013.11.008 kostenfrei https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 kostenfrei http://www.sciencedirect.com/science/article/pii/S1873506113001700 kostenfrei https://doaj.org/toc/1873-5061 Journal toc kostenfrei https://doaj.org/toc/1876-7753 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_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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2014 2 323-337
allfields_unstemmed	10.1016/j.scr.2013.11.008 doi (DE-627)DOAJ03348662X (DE-599)DOAJ9afed9bd1b1d496fab11a25aa8ee20b2 DE-627 ger DE-627 rakwb eng QH301-705.5 Antonietta Coppola verfasserin aut Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Biology (General) Antonio Romito verfasserin aut Christelle Borel verfasserin aut Corinne Gehrig verfasserin aut Maryline Gagnebin verfasserin aut Emilie Falconnet verfasserin aut Antonella Izzo verfasserin aut Lucia Altucci verfasserin aut Sandro Banfi verfasserin aut Stylianos E. Antonarakis verfasserin aut Gabriella Minchiotti verfasserin aut Gilda Cobellis verfasserin aut In Stem Cell Research Elsevier, 2015 12(2014), 2, Seite 323-337 (DE-627)548125856 (DE-600)2393143-7 18767753 nnns volume:12 year:2014 number:2 pages:323-337 https://doi.org/10.1016/j.scr.2013.11.008 kostenfrei https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 kostenfrei http://www.sciencedirect.com/science/article/pii/S1873506113001700 kostenfrei https://doaj.org/toc/1873-5061 Journal toc kostenfrei https://doaj.org/toc/1876-7753 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_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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2014 2 323-337
allfieldsGer	10.1016/j.scr.2013.11.008 doi (DE-627)DOAJ03348662X (DE-599)DOAJ9afed9bd1b1d496fab11a25aa8ee20b2 DE-627 ger DE-627 rakwb eng QH301-705.5 Antonietta Coppola verfasserin aut Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Biology (General) Antonio Romito verfasserin aut Christelle Borel verfasserin aut Corinne Gehrig verfasserin aut Maryline Gagnebin verfasserin aut Emilie Falconnet verfasserin aut Antonella Izzo verfasserin aut Lucia Altucci verfasserin aut Sandro Banfi verfasserin aut Stylianos E. Antonarakis verfasserin aut Gabriella Minchiotti verfasserin aut Gilda Cobellis verfasserin aut In Stem Cell Research Elsevier, 2015 12(2014), 2, Seite 323-337 (DE-627)548125856 (DE-600)2393143-7 18767753 nnns volume:12 year:2014 number:2 pages:323-337 https://doi.org/10.1016/j.scr.2013.11.008 kostenfrei https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 kostenfrei http://www.sciencedirect.com/science/article/pii/S1873506113001700 kostenfrei https://doaj.org/toc/1873-5061 Journal toc kostenfrei https://doaj.org/toc/1876-7753 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_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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2014 2 323-337
allfieldsSound	10.1016/j.scr.2013.11.008 doi (DE-627)DOAJ03348662X (DE-599)DOAJ9afed9bd1b1d496fab11a25aa8ee20b2 DE-627 ger DE-627 rakwb eng QH301-705.5 Antonietta Coppola verfasserin aut Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. Biology (General) Antonio Romito verfasserin aut Christelle Borel verfasserin aut Corinne Gehrig verfasserin aut Maryline Gagnebin verfasserin aut Emilie Falconnet verfasserin aut Antonella Izzo verfasserin aut Lucia Altucci verfasserin aut Sandro Banfi verfasserin aut Stylianos E. Antonarakis verfasserin aut Gabriella Minchiotti verfasserin aut Gilda Cobellis verfasserin aut In Stem Cell Research Elsevier, 2015 12(2014), 2, Seite 323-337 (DE-627)548125856 (DE-600)2393143-7 18767753 nnns volume:12 year:2014 number:2 pages:323-337 https://doi.org/10.1016/j.scr.2013.11.008 kostenfrei https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 kostenfrei http://www.sciencedirect.com/science/article/pii/S1873506113001700 kostenfrei https://doaj.org/toc/1873-5061 Journal toc kostenfrei https://doaj.org/toc/1876-7753 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_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_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 12 2014 2 323-337
language	English
source	In Stem Cell Research 12(2014), 2, Seite 323-337 volume:12 year:2014 number:2 pages:323-337
sourceStr	In Stem Cell Research 12(2014), 2, Seite 323-337 volume:12 year:2014 number:2 pages:323-337
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Biology (General)
isfreeaccess_bool	true
container_title	Stem Cell Research
authorswithroles_txt_mv	Antonietta Coppola @@aut@@ Antonio Romito @@aut@@ Christelle Borel @@aut@@ Corinne Gehrig @@aut@@ Maryline Gagnebin @@aut@@ Emilie Falconnet @@aut@@ Antonella Izzo @@aut@@ Lucia Altucci @@aut@@ Sandro Banfi @@aut@@ Stylianos E. Antonarakis @@aut@@ Gabriella Minchiotti @@aut@@ Gilda Cobellis @@aut@@
publishDateDaySort_date	2014-01-01T00:00:00Z
hierarchy_top_id	548125856
id	DOAJ03348662X
language_de	englisch
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callnumber-first	Q - Science
author	Antonietta Coppola
spellingShingle	Antonietta Coppola misc QH301-705.5 misc Biology (General) Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
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topic_title	QH301-705.5 Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
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title	Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
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title_full	Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
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author_browse	Antonietta Coppola Antonio Romito Christelle Borel Corinne Gehrig Maryline Gagnebin Emilie Falconnet Antonella Izzo Lucia Altucci Sandro Banfi Stylianos E. Antonarakis Gabriella Minchiotti Gilda Cobellis
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title_sort	cardiomyogenesis is controlled by the mir-99a/let-7c cluster and epigenetic modifications
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title_auth	Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
abstract	Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis.
abstractGer	Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis.
abstract_unstemmed	Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis.
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title_short	Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications
url	https://doi.org/10.1016/j.scr.2013.11.008 https://doaj.org/article/9afed9bd1b1d496fab11a25aa8ee20b2 http://www.sciencedirect.com/science/article/pii/S1873506113001700 https://doaj.org/toc/1873-5061 https://doaj.org/toc/1876-7753
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up_date	2024-07-03T18:01:19.597Z
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Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications

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