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

Item Type:Article
Title:Dynamics of Srf, p300 and histone modifications during cardiac maturation in mouse
Creators Name:Schueler, M. and Zhang, Q. and Schlesinger, J. and Toenjes, M. and Sperling, S.R.
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.
Keywords:Acetylation, Cardiac Myocytes, Cell Line, Chromatin Immunoprecipitation, Developmenta lGene Expression Regulation, DNA, E1A-Associated p300 Protein, Genetic Promoter Regions, Genetic Transcription, Heart, Histones, Messenger RNA, Methylation, Post-Translational Protein Processing, Serum Response Factor, Transcriptional Activation, Animals, Mice
Source:Molecular BioSystems
Publisher:Royal Society of Chemistry
Page Range:495-503
Date:February 2012
Official Publication:https://doi.org/10.1039/c1mb05363a
PubMed:View item in PubMed

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