Identification of a CArG box-dependent enhancer within the cysteine-rich protein 1 gene that directs expression in arterial but not venous or visceral smooth muscle cells

Brenda Lilly, Eric N. Olson, Mary C. Beckerle

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Smooth muscle cells (SMCs) are heterogeneous with respect to their contractile, synthetic, and proliferative properties, though the regulatory factors responsible for their phenotypic diversity remain largely unknown. To further our understanding of smooth muscle gene regulation, we characterized the cis-regulatory elements of the murine cysteine-rich protein 1 gene (CRP1/Csrp1). CRP1 is expressed in all muscle cell types during embryogenesis and predominates in vascular and visceral SMCs in the adult. We identified a 5-kb enhancer within the CRP1 gene that is sufficient to drive expression in arterial but not venous or visceral SMCs in transgenic mice. This enhancer also exhibits region-specific activity in the outflow tract of the heart and the somites. Within the 5-kb CRP1 enhancer, we found a single CArG box that binds serum response factor (SRF), and by mutational analysis, demonstrate that the activity of the enhancer is dependent on this CArG element. Our findings provide further evidence for the existence of distinct regulatory programs within SMCs and suggest a role for SRF in the activation of the CRP1 gene.

Original languageEnglish (US)
Pages (from-to)531-547
Number of pages17
JournalDevelopmental Biology
Volume240
Issue number2
DOIs
StatePublished - Dec 15 2001

Keywords

  • CArG
  • CRP1
  • Csrp1
  • Cysteine-rich protein
  • SRF
  • Smooth muscle
  • Vascular

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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