Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Identification of transcription factor Srf binding sites and histone 3 actetylated regions in mouse cardiomyocytes

ABSTRACT: We investigated the cardiac transcription network driven by the DNA-binding key factor Srf in combination with epigenetic marks of histone 3 acetylation (H3ac). Srf has been shown to play a key role in cardiac cell growth and muscle gene regulation. However, we still have limited understanding of the global transcription network driven by this factor in a direct or indirect manner. Moreover, we lack knowledge to which extent epigenetic marks such as histone modifications interfere with the regulation of direct targets. To gain insights into the transcriptional regulatory network two independent chromatin immunoprecipitation (ChIP) samples were profiled. DNA fragments bound to Srf or modified with acetylated histone 3 in mouse cardiomyocytes (HL1-cells) were sequenced using ultra-high throughput DNA sequencing. ChIP-seq profile of a transcription factor (Srf) and a histone modification (H3ac)

ORGANISM(S): Mus musculus

SUBMITTER: Silke Sperling

PROVIDER: E-GEOD-19065 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs.

Schlesinger Jenny J Schueler Markus M Grunert Marcel M Fischer Jenny J JJ Zhang Qin Q Krueger Tammo T Lange Martin M Tönjes Martje M Dunkel Ilona I Sperling Silke R SR

PLoS genetics 20110217 2

The transcriptome, as the pool of all transcribed elements in a given cell, is regulated by the interaction between different molecular levels, involving epigenetic, transcriptional, and post-transcriptional mechanisms. However, many previous studies investigated each of these levels individually, and little is known about their interdependency. We present a systems biology study integrating mRNA profiles with DNA-binding events of key cardiac transcription factors (Gata4, Mef2a, Nkx2.5, and Srf ...[more]

PMID: 21379568

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Project description:To identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this “cardiac aging” model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function. The generation and characterization of transgenic mice with mild cardiac-specific overexpression of SRF was previously reported (Zhang et al., 2003). At 6 months of age, the transgenic mice manifested cardiac changes suggestive of an “aged heart” (Zhang et al., 2003). Therefore, 6-month-old transgenic and non-transgenic mice were used in this study. Cardiac gene expression in SRF Tg heart was compared to that of wild-type mice.

Dataset Information

Identification of transcription factor Srf binding sites and histone 3 actetylated regions in mouse cardiomyocytes

Publications

The cardiac transcription network modulated by Gata4, Mef2a, Nkx2.5, Srf, histone modifications, and microRNAs.

Similar Datasets

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