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  • Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.

Epigenetic response to environmental stress: Assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.

Biochimica et biophysica acta (2016-03-10)
Pei Han, Wei Li, Jin Yang, Ching Shang, Chiou-Hong Lin, Wei Cheng, Calvin T Hang, Hsiu-Ling Cheng, Chen-Hao Chen, Johnson Wong, Yiqin Xiong, Mingming Zhao, Stavros G Drakos, Andrea Ghetti, Dean Y Li, Daniel Bernstein, Huei-Sheng Vincent Chen, Thomas Quertermous, Ching-Pin Chang
ABSTRACT

Chromatin structure is determined by nucleosome positioning, histone modifications, and DNA methylation. How chromatin modifications are coordinately altered under pathological conditions remains elusive. Here we describe a stress-activated mechanism of concerted chromatin modification in the heart. In mice, pathological stress activates cardiomyocytes to express Brg1 (nucleosome-remodeling factor), G9a/Glp (histone methyltransferase), and Dnmt3 (DNA methyltransferase). Once activated, Brg1 recruits G9a and then Dnmt3 to sequentially assemble repressive chromatin-marked by H3K9 and CpG methylation-on a key molecular motor gene (Myh6), thereby silencing Myh6 and impairing cardiac contraction. Disruption of Brg1, G9a or Dnmt3 erases repressive chromatin marks and de-represses Myh6, reducing stress-induced cardiac dysfunction. In human hypertrophic hearts, BRG1-G9a/GLP-DNMT3 complex is also activated; its level correlates with H3K9/CpG methylation, Myh6 repression, and cardiomyopathy. Our studies demonstrate a new mechanism of chromatin assembly in stressed hearts and novel therapeutic targets for restoring Myh6 and ventricular function. The stress-induced Brg1-G9a-Dnmt3 interactions and sequence of repressive chromatin assembly on Myh6 illustrates a molecular mechanism by which the heart epigenetically responds to environmental signals. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-G9a Methyltransferase antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Pricing and availability is not currently available.
Sigma-Aldrich
ChIPAb+ Dimethyl-Histone H3 (Lys9) - ChIP Validated Antibody and Primer Set, serum, from rabbit
Pricing and availability is not currently available.