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  Dynamics of Srf, p300 and histone modifications during cardiac maturation in mouse

Schueler, M., Zhang, Q., Schlesinger, J., Tönjes, M., & Sperling, S. (2012). Dynamics of Srf, p300 and histone modifications during cardiac maturation in mouse. Molecular BioSystems, 8(2), 495-503. doi:10.1039/c1mb05363a.

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Schueler, Markus1, Author           
Zhang, Q., Author
Schlesinger, Jenny1, Author           
Tönjes, Martje1, Author           
Sperling, Silke1, Author           
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1Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              

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Free keywords: Acetylation Animals Cell Line Chromatin Immunoprecipitation/methods DNA/metabolism E1A-Associated p300 Protein/*metabolism Gene Expression Regulation, Developmental Heart/*embryology Histones/*metabolism Methylation Mice Myocytes, Cardiac/metabolism Promoter Regions, Genetic Protein Processing, Post-Translational RNA, Messenger/biosynthesis Serum Response Factor/*metabolism Transcription, Genetic Transcriptional Activation
 Abstract: The adaptation of the cellular network to functional changes, timing and patterning of gene expression is regulated by binding of transcription factors to gene regulatory elements, which in turn depends on co-occurring histone modifications. These two layers influence each other, enabling a further level of regulatory fine-tuning. We analyzed the interdependencies between histone 3 acetylation, histone 3 lysine 4 dimethylation, the transcription factor Srf and the histone acetyltransferase p300 in an in vivo model using chromatin immunoprecipitation in a time-series during cardiac maturation in mouse. We found a strong correlation between the presence of the two histone modifications and binding of Srf and p300. Using linear modeling techniques we could show that each factor contributes individually as well as conjointly to histone 3 acetylation and gene expression, probably aided by accompanying histone 3 lysine 4 dimethylation. We further demonstrate that changes in gene expression during cardiac maturation are attended by changes of the analyzed regulators while revealing a high variability of combinatorial regulation. Finally, we propose a model of Srf-driven gene expression in cardiomyocytes.

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Language(s): eng - English
 Dates: 2012-02
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1039/c1mb05363a
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Title: Molecular BioSystems
Source Genre: Journal
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Publ. Info: Cambridge, UK : Royal Society of Chemistry
Pages: - Volume / Issue: 8 (2) Sequence Number: - Start / End Page: 495 - 503 Identifier: ISSN: 1742-206X
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000023020