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Published on: June 3, 2018
Identification of a novel serum response factor cofactor in cardiac gene regulation
Xiaomin Zhang1, Gohar Azhar, Ying Zhong
1Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences and Geriatric Research, 4301 W. Markham #748, Little Rock, AR 72205, USA.
Abstract:
The transcription factor serum response factor (SRF) plays an important role in the regulation of a variety of cardiac genes during development and during adult aging. A novel SRF cofactor, herein called p49/STRAP, for SRF-dependent transcription regulation-associated protein, was recently identified in our laboratory. This protein interacted mainly with the transcriptional activation domain of the SRF protein and was found to bind to SRF or to the complex of SRF and another cofactor, such as myocardin or Nkx2.5. The expression of p49/STRAP affected the promoter activity of SRF target genes in a non-uniform manner. For example, p49 activated MLC2v and cardiac actin promoters when it was co-transfected with SRF, but it repressed atrial natriuretic factor promoter activity, which was strongly induced by myocardin. The p49/STRAP mRNA was observed to be highly expressed in fetal, adult, and senescent human hearts, and also in hearts of young adult and old mice, suggesting that p49/STRAP may be an important SRF cofactor in the transcriptional regulation of mammalian cardiac muscle genes throughout the life span.
Insights
A newly identified protein, p49/STRAP, acts as a cofactor for serum response factor (SRF) in regulating cardiac genes. This protein
Area of Science:
- Molecular Biology
- Cardiovascular Biology
- Gene Regulation
Background:
- Serum response factor (SRF) is crucial for cardiac gene regulation during development and aging.
- A novel SRF cofactor, p49/STRAP (SRF-dependent transcription regulation-associated protein), has been identified.
Purpose of the Study:
- To investigate the role and function of the novel SRF cofactor, p49/STRAP.
- To determine the impact of p49/STRAP on SRF-mediated transcriptional activity in cardiac genes.
Main Methods:
- Co-transfection assays to study the interaction between p49/STRAP, SRF, and other cofactors (myocardin, Nkx2.5).
- Analysis of promoter activity of SRF target genes (MLC2v, cardiac actin, atrial natriuretic factor).
- Quantitative analysis of p49/STRAP mRNA expression in human and mouse heart tissues across different life stages.
Main Results:
- p49/STRAP interacts with the transcriptional activation domain of SRF.
- p49/STRAP exhibits differential effects on SRF target gene promoters: activation of MLC2v and cardiac actin, but repression of atrial natriuretic factor.
- p49/STRAP mRNA is highly expressed in human and mouse hearts throughout development and aging.
Conclusions:
- p49/STRAP functions as a significant cofactor for SRF in regulating cardiac gene expression.
- The differential regulatory effects of p49/STRAP suggest a complex role in cardiac transcriptional control.
- p49/STRAP is likely important for mammalian cardiac muscle gene regulation across the lifespan.
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