The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF

被引：137

作者：

Philippar, U

Schratt, G

Dieterich, C

Müller, JM

Galgóczy, P

Engel, FB

Keating, MT

Gertler, F

Schüle, R

Vingron, M

Nordheim, A ^{[1
]}

机构：

[1] Univ Tubingen, Inst Zellbiol, Mol Biol Abt, D-72076 Tubingen, Germany

[2] Max Planck Inst Mol Genet, Berlin, Germany

[3] Univ Freiburg Klinikum, Frauenklin, Zent Klin Forschung, D-79106 Freiburg, Germany

[4] Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Dept Cell Biol, Boston, MA 02115 USA

[5] MIT, Dept Biol, Cambridge, MA 02139 USA

来源：

MOLECULAR CELL | 2004年 / 16卷 / 06期

关键词：

D O I：

10.1016/j.molcel.2004.11.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RhoA signaling regulates the activity of the transcription factor SRF (serum response factor) during muscle differentiation. How RhoA signaling is integrated at SRF target promoters to achieve muscle-lineage-specific expression is largely unknown. Using large-scale expression profiling combined with bioinformatic and biochemical approaches, we identified several SRF target genes, including FhI2, encoding a transcriptional cofactor that is highly expressed in the heart. SRF binds the FhI2 promoter in vivo and regulates FhI2 expression in response to RhoA activation. FHL2 protein and SRF interact physically, and FHL2 binds the promoters of SRF-responsive smooth muscle (SM) genes, but not the promoters of immediate-early genes (IEGs), in response to RhoA. FHL2 antagonizes induction of SM genes, but not IEGs or cardiac genes, by competing with the coactivator MAL/MRTF-A for SRF binding. Our findings identify an autoregulatory mechanism to selectively regulate subsets of RhoA-activated SRF target genes.

引用

页码：867 / 880

页数：14

共 34 条

[11]

Kong YF, 2001, CIRCULATION, V103, P2731

[12] CArG elements control smooth muscle subtype-specific expression of smooth muscle myosin in vivo [J].