Myocyte nuclear factor, a novel winged-helix transcription factor under both developmental and neural regulation in striated myocytes

Rhonda Bassel-Duby, Maria D. Hernandez, Quan Yang, Julie M. Rochelle, Michael F. Seldin, R. Sanders Williams

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

A sequence motif (CCAC box) within an upstream enhancer region of the human myoglobin gene is essential for transcriptional activity in both cardiac and skeletal muscle. A cDNA clone, myocyte nuclear factor (MNF), was isolated from a murine expression library on the basis of sequence-specific binding to the myoglobin CCAC box motif and was found to encode a novel member of the winged-helix or HNF-3/fork head family of transcription factors. Probes based on this sequence identify two mRNA species that are upregulated during myocyte differentiation, and antibodies raised against recombinant MNF identify proteins of approximately 90, 68, and 65 kDa whose expression is regulated following differentiation of myogenic cells in culture. In addition, the 90-kDa form of MNF is phosphorylated and is upregulated in intact muscles subjected to chronic motor nerve stimulation, a potent stimulus to myoglobin gene regulation. Amino acid residues 280 to 389 of MNF demonstrate 35 to 89% sequence identify to the winged-helix domain from other known members of this family, but MNF is otherwise divergent. A proline-rich amino-terminal region (residues 1 to 206) of MNF functions as a transcriptional activation domain. These studies provide the first evidence that members of the winged-helix family of transcription factors have a role in myogenic differentiation and in remodeling processes of adult muscles that occur in response to physiological stimuli.

Original languageEnglish (US)
Pages (from-to)4596-4605
Number of pages10
JournalMolecular and cellular biology
Volume14
Issue number7
DOIs
StatePublished - Jul 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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