Tbx1 represses Mef2c gene expression and is correlated with histone 3 deacetylation of the anterior heart field enhancer
| Autor: | Alessandra Altomonte, Luna Simona Pane, Andrea Cirino, Rosa Ferrentino, Filomena Gabriella Fulcoli, Marchesa Bilio, Antonio Baldini |
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| Přispěvatelé: | Pane, Luna Simona, Fulcoli, Filomena Gabriella, Cirino, Andrea, Altomonte, Alessandra, Ferrentino, Rosa, Bilio, Marchesa, Baldini, Antonio |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Medicine (miscellaneous) lcsh:Medicine Histones 0302 clinical medicine Immunology and Microbiology (miscellaneous) MEF2C Gene MEF2C MEF2 Transcription Factors Gene Expression Regulation Developmental Acetylation Cell Differentiation Heart Tbx1 Cell biology Anterior heart field enhancer Mef2c Histone Enhancer Elements Genetic embryonic structures Female Research Article lcsh:RB1-214 TBX1 Transgene Induced Pluripotent Stem Cells Neuroscience (miscellaneous) Mice Transgenic Biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences stomatognathic system DiGeorge Syndrome lcsh:Pathology Animals Humans Enhancer Transcription factor Biochemistry Genetics and Molecular Biology (all) Base Sequence Myocardium lcsh:R Embryo Mammalian GATA4 Transcription Factor 030104 developmental biology biology.protein T-Box Domain Proteins 030217 neurology & neurosurgery |
| Zdroj: | Disease Models & Mechanisms, Vol 11, Iss 9 (2018) Disease models & mechanisms 11 (2018). doi:10.1242/dmm.029967 info:cnr-pdr/source/autori:Pane L.S.; Fulcoli F.G.; Cirino A.; Altomonte A.; Ferrentino R.; Bilio M.; Baldini A./titolo:Tbx1 represses Mef2c gene expression and is correlated with histone 3 deacetylation of the anterior heart field enhancer/doi:10.1242%2Fdmm.029967/rivista:Disease models & mechanisms (Print)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume:11 Disease Models & Mechanisms |
| ISSN: | 1754-8411 1754-8403 |
| DOI: | 10.1242/dmm.029967 |
| Popis: | The TBX1 gene is haploinsufficient in 22q11.2 deletion syndrome (22q11.2DS), and genetic evidence from human patients and mouse models points to a major role of this gene in the pathogenesis of this syndrome. Tbx1 can activate and repress transcription, and previous work has shown that one of its functions is to negatively modulate cardiomyocyte differentiation. Tbx1 occupies the anterior heart field (AHF) enhancer of the Mef2c gene, which encodes a key cardiac differentiation transcription factor. Here, we show that increased dosage of Tbx1 correlates with downregulation of Mef2c expression and reduced acetylation of its AHF enhancer in cultured mouse myoblasts. Consistently, 22q11.2DS-derived and in vitro-differentiated human induced pluripotent stem cells (hiPSCs) expressed higher levels of MEF2C and showed increased AHF acetylation, compared with hiPSCs from a healthy donor. Most importantly, we show that in mouse embryos, loss of Tbx1 enhances the expression of the Mef2c-AHF-Cre transgene in a specific region of the splanchnic mesoderm, and in a dosage-dependent manner, providing an in vivo correlate of our cell culture data. These results indicate that Tbx1 regulates the Mef2c AHF enhancer by inducing histone deacetylation. Summary: Using three experimental models, we demonstrate that Tbx1 suppresses Mef2c gene expression, and show that histone 3 acetylation of the anterior heart field enhancer of the Mef2c gene responds negatively to Tbx1 dosage. |
| Databáze: | OpenAIRE |
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