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

Philippar, Ulrike; Schratt, Gerhard; Dieterich, Christoph; Müller, Judith M.; Galgóczy, Petra; Engel, Felix B.; Keating, Mark T.; Gertler, Frank; Schüle, Roland; Vingron, Martin; Nordheim, Alfred

doi:10.1016/j.molcel.2004.11.039

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

Philippar, U., Schratt, G., Dieterich, C., Müller, J. M., Galgóczy, P., Engel, F. B., et al. (2004). The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF. Molecular Cell, 16(12), 867-880. doi:10.1016/j.molcel.2004.11.039.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-876F-1 Version Permalink: https://hdl.handle.net/11858/00-001M-0000-0010-8770-C

Genre: Journal Article

Alternative Title : Mol Cell

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Creators:
Philippar, Ulrike, Author
Schratt, Gerhard, Author
Dieterich, Christoph¹, Author
Müller, Judith M., Author
Galgóczy, Petra, Author
Engel, Felix B., Author
Keating, Mark T., Author
Gertler, Frank, Author
Schüle, Roland, Author
Vingron, Martin², Author
Nordheim, Alfred, Author

Affiliations:
1Max Planck Society, ou_persistent13
2Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639

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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.

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Language(s): eng - English

Dates: Date issued: 2004-12-22

Publication Status: Issued

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Identifiers: eDoc: 228590
DOI: 10.1016/j.molcel.2004.11.039

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Title: Molecular Cell

Alternative Title : Mol Cell

Source Genre: Journal

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Pages: - Volume / Issue: 16 (12) Sequence Number: - Start / End Page: 867 - 880 Identifier: ISSN: 1097-2765