Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/12505
Title: Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4.
Authors: Ounzain, S
Kobayashi, S
Peterson, RE
He, A
Motterle, A
Samani, NJ
Menick, DR
Pu, WT
Liang, Q
Chong, NW
First Published: May-2012
Citation: MOL CELL BIOL, 2012, 32 (10), pp. 1830-1843
Abstract: Ms1/STARS is a novel muscle-specific actin-binding protein that specifically modulates the myocardin-related transcription factor (MRTF)-serum response factor (SRF) regulatory axis within striated muscle. This ms1/STARS-dependent regulatory axis is of central importance within the cardiac gene regulatory network and has been implicated in cardiac development and postnatal cardiac function/homeostasis. The dysregulation of ms1/STARS is associated with and causative of pathological cardiac phenotypes, including cardiac hypertrophy and cardiomyopathy. In order to gain an understanding of the mechanisms governing ms1/STARS expression in the heart, we have coupled a comparative genomic in silico analysis with reporter, gain-of-function, and loss-of-function approaches. Through this integrated analysis, we have identified three evolutionarily conserved regions (ECRs), α, SINA, and DINA, that act as cis-regulatory modules and confer differential cardiac cell-specific activity. Two of these ECRs, α and DINA, displayed distinct regulatory sensitivity to the core cardiac transcription factor GATA4. Overall, our results demonstrate that within embryonic, neonatal, and adult hearts, GATA4 represses ms1/STARS expression with the pathologically associated depletion of GATA4 (type 1/type 2 diabetic models), resulting in ms1/STARS upregulation. This GATA4-dependent repression of ms1/STARS expression has major implications for MRTF-SRF signaling in the context of cardiac development and disease.
DOI Link: 10.1128/MCB.06374-11
eISSN: 1098-5549
Links: http://hdl.handle.net/2381/12505
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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