Journal article
The Histone Demethylase, Jmjd1a, Interacts With the Myocardin Factors to Regulate SMC Differentiation Marker Gene Expression
Circulation research, Vol.101(12), pp.e115-e123
12/07/2007
DOI: 10.1161/CIRCRESAHA.107.164178
PMID: 17991879
Abstract
We and others have previously shown that the myocardin transcription factors play critical roles in the regulation of smooth muscle cell (SMC) differentiation marker gene expression. In a yeast 2-hybrid screen for proteins that interact with myocardin-related transcription factor-A (MRTF-A), we identified the histone 3 lysine 9 (H3K9)-specific demethylase, Jmjd1a. GST pull-down assays demonstrated that Jmjd1a bound all 3 myocardin family members, and further mapping studies showed that the jumonjiC domain of Jmjd1a was sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreased global levels of di-methyl H3K9, stimulated the SM alpha-actin and SM22 promoters, and synergistically enhanced MRTF-A- and myocardin-dependent transactivation. Using chromatin immunoprecipitation assays, we also demonstrated that TGF-beta-mediated upregulation of SMC differentiation marker gene expression in 10T1/2 cells was associated with decreased H3K9 dimethylation at the CArG-containing regions of the SMC differentiation marker gene promoters. Importantly, knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic SMCs by retroviral delivery of siRNA attenuated TGF-beta-induced upregulation of endogenous SM myosin heavy chain expression. These effects were concomitant with increased H3K9 dimethylation at the SMC differentiation marker gene promoters and with inhibition of MRTF-A-dependent transactivation of the SMC-specific transcription. These results suggest, for the first time, that SMC differentiation marker gene expression is regulated by H3K9 methylation and that the effects of the myocardin factors on SMC-specific transcription may involve the recruitment of Jmjd1a to the SMC-specific promoters.
Details
- Title: Subtitle
- The Histone Demethylase, Jmjd1a, Interacts With the Myocardin Factors to Regulate SMC Differentiation Marker Gene Expression
- Creators
- Kashelle Lockman - From the Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel HillJoan M Taylor - From the Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel HillChristopher P Mack - From the Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.101(12), pp.e115-e123
- DOI
- 10.1161/CIRCRESAHA.107.164178
- PMID
- 17991879
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 12/07/2007
- Academic Unit
- Pharmacy Practice and Science; Office of Consultation and Research in Medical Education; Internal Medicine
- Record Identifier
- 9984065689002771
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