Transcriptomics

Dataset Information

20

Microarray analysis of heart gene expression in wild type and JMJD2A heart specific transgenic mice after sham and thoracic aortic constriction surgery


ABSTRACT: Cardiac hypertrophy and failure are accompanied by a reprogramming of gene expression that involves transcription factors and chromatin remodeling enzymes. Little is known about the role of histone methylation and demethylation in this process. To understand the role of JMJD2A, a trimethyl demethylase for histone 3 lysine 9 and 36, in cardiac hypertrophy, we generated heart specific JMJD2A deletion (JMJD2A hKO) and overexpression (JMJD2A-Tg) mouse lines. JMJD2A hKO and JMJD2A-Tg mice are viable and have no overt baseline phenotype. However, they have altered responses to cardiac stresses. While inactivation of JMJD2A in hKO mice resulted in an attenuated hypertrophic response to transverse aortic constriction (TAC)-induced pressure overload compared to that of control littermates, JMJD2A-Tg mice have exacerbated cardiac hypertrophy after TAC. We identified four-and-a-half LIM domains 1 (FHL1) as a novel target of JMJD2A. JMJD2A binds to the FHL1 promoter in response to TAC and upregulates the expression of FHL1. Binding of JMJD2A to the FHL1 promoter is associated with downregulation of trimethylated H3K9. Upregulation of FHL1 by JMJD2A is mediated through SRF and myocardin, and requires its demethylase activity. The expression of JMJD2A is upregulated in human hypertrophic cardiomyopathy patients. Our studies reveal that JMJD2A promotes cardiac hypertrophy by synergistically upregulating SRF/myocardin-targeted genes and suggest a novel mechanism of reprogramming of gene expression involved in cardiac hypertrophy. Overall design: Six to eight years old wildtype and JMJD2A heart specific transgnic mice were undergone either sham or TAC surgery. After 3 weeks, mice were sarcirificed to harvest heart. RNA was extracted from heart samples and treated with DNase, followed by biotin-labeling and microarray hybridization.

INSTRUMENT(S): Illumina MouseWG-6 v2.0 expression beadchip

ORGANISM(S): Mus musculus  

SUBMITTER: Qingjun Zhang   

PROVIDER: GSE27689 | GEO | 2011-06-02

SECONDARY ACCESSION(S): PRJNA138145

REPOSITORIES: GEO

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