Serum response factor: Toggling between disparate programs of gene expression

Joseph M. Miano

Research output: Contribution to journalReview article

Abstract

Serum response factor (SRF) is a widely expressed transcription factor involved in orchestrating disparate programs of gene expression linked to muscle differentiation and cellular growth. Vascular smooth muscle cell (SMC) differentiation, for example, is marked by the coordinate expression of several contractile and cytoskeletal genes regulated directly by SRF through one or more CArG-box elements in the immediate vicinity of transcription start sites. In vascular disease, this CArG-dependent program of SMC differentiation is compromised and numerous CArG-dependent early growth-response genes are activated. Thus, SRF must toggle between programs of SMC differentiation and growth depending on local environmental cues. Moreover, SRF must distinguish between a course of SMC differentiation and programs of cardiac and skeletal muscle differentiation. Several mechanisms exist to ensure context- and cell-specific programs of SRF-dependent gene expression. These include regulated expression, DNA binding, and alternative splicing of SRF, flanking sequences adjacent to and chromatin remodeling of CArG boxes, RhoA-mediated alterations in the cytoskeleton, and association of SRF with a variety of cell-restricted cofactors including the recently discovered myocardin coactivator. Although many SMC-differentiation genes require critical evolutionarily conserved CArG boxes for SMC-restricted promoter activity in cultured cells and transgenic mice, the expression of a growing number of similarly restricted genes appears to be independent of SRF. Thus, parallel circuits of gene transcription have evolved for the appropriate expression of all genes that define mammalian SMC lineages. The purpose of this review is to summarize the history and progress made in SRF research with emphasis on the role this transcription factor plays in facilitating a program of SMC-restricted gene expression.

Original languageEnglish (US)
Pages (from-to)577-593
Number of pages17
JournalJournal of molecular and cellular cardiology
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Serum Response Factor
Smooth Muscle Myocytes
Gene Expression
Cell Differentiation
Genes
Transcription Factors
Growth
Chromatin Assembly and Disassembly
Gene Regulatory Networks
Transcription Initiation Site
Alternative Splicing
Cell Lineage
Cytoskeleton
Vascular Diseases
Vascular Smooth Muscle
Transgenic Mice
Cues
Cultured Cells
Myocardium
Skeletal Muscle

Keywords

  • Bioinformatics
  • Calponin
  • Evolution
  • Genome
  • Integrin
  • Myocardin
  • Myosin
  • Promoter
  • SM22
  • Smooth muscle
  • Transgenic

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Serum response factor : Toggling between disparate programs of gene expression. / Miano, Joseph M.

In: Journal of molecular and cellular cardiology, Vol. 35, No. 6, 01.06.2003, p. 577-593.

Research output: Contribution to journalReview article

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