The SRF Target Gene Fhl2 Antagonizes RhoA/MAL-Dependent Activation of SRF
Name
Gertler_The SRF target.pdf
Size
815.61 KB
Format
Adobe PDF
Checksum (MD5)
131bee72730a5d8d1856a11eda4663ce
Author(s)
Philippar, Ulrike
Schratt, Gerhard
Dieterich, Christoph
Engel, Felix B.
Keating, Mark T.
Gertler, Frank
Vingron, Martin
Nordheim, Alfred
Galgoczy, Petra
Schule, Roland
Date Issued
December 2004
Journal
Molecular Cell
Publisher
Elsevier
Citation
Philippar, Ulrike, Gerhard Schratt, Christoph Dieterich, Judith M. Müller, Petra Galgóczy, Felix B. Engel, Mark T. Keating, et al. “The SRF Target Gene Fhl2 Antagonizes RhoA/MAL-Dependent Activation of SRF.” Molecular Cell 16, no. 6 (December 2004): 867-880. Copyright © 2004 Cell Press
Version
Final published version
Abstract
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 Fhl2, encoding a transcriptional cofactor that is highly expressed in the heart. SRF binds the Fhl2 promoter in vivo and regulates Fhl2 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.molcel.2004.11.039
