A triad of serum response factor and the GATA and NK families governs the transcription of smooth and cardiac muscle genes

Wataru Nishida, Mako Nakamura, Syunsuke Mori, Masanori Takahashi, Yasuyuki Ohkawa, Satoko Tadokoro, Kenji Yoshida, Kunio Hiwada, Ke N.Ichiro Hayashi, Kenji Sobue

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

Serum response factor and the (CC(A/T)6GG) (CArG) box interact to promote the transcription of c-fos and muscle genes; this tissue-specific activity may require co-regulators for serum response factor. The α1 integrin promoter contains two cis-elements besides the CArG box: a TAAT sequence, a consensus binding site for homeoproteins, and a GATA-binding box. As a candidate TAAT-binding factor, we cloned an NK family homeobox gene, Nkx-3.2, which is expressed mainly in smooth muscle tissues and skeletal structures. Nkx-3.2, serum response factor, and GATA-6 were co-expressed only in the medial smooth muscle layer of arteries. These three transcription factors formed a complex with their corresponding cis-elements and cooperatively transactivated smooth muscle genes, including α1 integrin, SM22α, and caldesmon. Cardiac muscle-specific members of the NK and GATA families exist, and the triad of Nkx-2.5, serum response factor, and GATA-4 also transactivated the cardiac atrial natriuretic factor gene, which contains a CArG-like box, a GATA-binding box, and an NK-binding element. Our findings demonstrate that smooth and cardiac muscle have a shared transcriptional machinery and that the GATA and NK families confer muscle specificity on the serum response factor/CArG interaction.

Original languageEnglish
Pages (from-to)7308-7317
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number9
DOIs
Publication statusPublished - Mar 1 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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