Genome-wide occupancy profile of Tbx3, Gata4, Nkx2-5 and p300 in adult mouse whole heart
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE35151 | GEO | 2012/06/22
SECONDARY ACCESSION(S): PRJNA150771
REPOSITORIES: GEO
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Project description:The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system–regulating transcription factors TBX3, NKX2-5, and GATA4 and of enhancer-associated coactivator p300 in the mouse heart, uncovering cardiac enhancers throughout the genome. Examination of 3 cardiac transcription factors and p300 in adult mouse heart
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Project description:The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system–regulating transcription factors TBX3 in the mouse heart, uncovering cardiac enhancers throughout the genome. Examination of the cardiac transcription factor Tbx3 in adult mouse heart
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Project description:The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system–regulating transcription factors TBX3 in the mouse heart, uncovering cardiac enhancers throughout the genome.
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Project description:Sudden cardiac death is the number one cause of death worldwide. Major causes of sudden cardiac death include myocardial infarction and cardiomyopathies. To develop novel therapeutic strategies, we need to identify key factors that are required for proper cardiac function and are dysregulated in the diseased heart. Under this notion, we found T-box 5 (TBX5), a transcription factor regarded solely in the context of congenital heart disease, to be downregulated in human diseased left ventricles. To investigate the effects of TBX5 loss in the adult heart, we generated an inducible ventricular cardiomyocyte specific knock-out mouse model (vTbx5KO). We performed integrative genome-wide chromatin occupancy and transcriptomic analysis and identified 47 downregulated transcripts in vTbx5KO that contain TBX5 active enhancers. The TBX5 targets in the ventricle included genes implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5) as well as cardiac protection upon stress (Fhl2, Gpr22, Fgf16). In line with this analysis, vTbx5KO mice presented cardiac conduction defects and arrhythmias at baseline as well as exacerbated cardiac remodeling upon Angiotensin II-induced hypertrophy. In conclusion, this study uncovers a novel protective role of TBX5 upon cardiac remodeling and renders TBX5 as an interesting therapeutic target.
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