The smooth muscle γ-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor

James Carson, Rebecca A. Fillmore, Robert J. Schwartz, Warren E. Zimmer

Research output: Contribution to journalArticle

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Abstract

An evolutionarily conserved vertebrate homologue of the Drosophila NK-3 homeodomain gene bagpipe, Nkx3-1, is expressed in vascular and visceral mesoderm-derived muscle tissues and may influence smooth muscle cell differentiation. Nkx3-1 was evaluated for mediating smooth muscle γ-actin (SMGA) gene activity, a specific marker of smooth muscle differentiation. Expression of mNkx3-1 in heterologous CV-1 fibroblasts was unable to elicit SMGA promoter activity but required the coexpression of serum response factor (SRF) to activate robust SMGA transcription. A novel complex element containing a juxtaposed Nkx-binding site (NKE) and an SRF-binding element (SRE) in the proximal promoter region was found to be necessary for the Nkx3-1/SRF coactivation of SMGA transcription. Furthermore, Nkx3-1 and SRF associate through protein-protein interactions and the homeodomain region of Nkx3-1 facilitated SRF binding to the complex NKE-SRE. Mutagenesis of Nkx3-1 revealed an inhibitory domain within its C-terminal segment. In addition, mNkx3-1/SRF cooperative activity required an intact Nkx3-1 homeodomain along with the MADS box of SRF, which contains DNA binding and dimerization structural domains, and the contiguous C-terminal SRF activation domain. Thus, SMGA is a novel target for Nkx3-1, and the activity of Nkx3-1 on the SMGA promoter is dependent upon SRF.

Original languageEnglish (US)
Pages (from-to)39061-39072
Number of pages12
JournalJournal of Biological Chemistry
Volume275
Issue number50
DOIs
StatePublished - Dec 15 2000

Fingerprint

Serum Response Factor
Smooth Muscle
Muscle
Actins
Genes
Transcription
Homeodomain Proteins
Mutagenesis
Dimerization
Mesoderm
Fibroblasts
Genetic Promoter Regions
Drosophila
Smooth Muscle Myocytes
Blood Vessels
Vertebrates
Cell Differentiation
Proteins
Chemical activation
Binding Sites

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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The smooth muscle γ-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor. / Carson, James; Fillmore, Rebecca A.; Schwartz, Robert J.; Zimmer, Warren E.

In: Journal of Biological Chemistry, Vol. 275, No. 50, 15.12.2000, p. 39061-39072.

Research output: Contribution to journalArticle

Carson, James ; Fillmore, Rebecca A. ; Schwartz, Robert J. ; Zimmer, Warren E. / The smooth muscle γ-actin gene promoter is a molecular target for the mouse bagpipe homologue, mNkx3-1, and serum response factor. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 50. pp. 39061-39072.
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