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

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.

journal_name

Mol Biosyst

journal_title

Molecular bioSystems

authors

Schueler M,Zhang Q,Schlesinger J,Tönjes M,Sperling SR

doi

10.1039/c1mb05363a

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

495-503

issue

2

eissn

1742-206X

issn

1742-2051

journal_volume

8

pub_type

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