Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter

J. Grayson, R. S. Williams, Y. T. Yu, R. Bassel-Duby

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Previous investigations have defined three upstream activation element- CAC, A/T, and TATA sequences-necessary for muscle-specific transcription of the myoglobin gene. In the present study, we demonstrate that these three sequence elements, prepared as synthetic oligonucleotide cassettes, function synergistically to constitute a cell-type-specific transcription unit. Previously, cognate binding factors that recognize the CCAC and TATA elements were identified. In this study we determine that the A/T element binds two nuclear factors, including myocyte enhancer factor-2 (MEF-2) and an apparently unknown factor we provisionally termed ATF35 (A/T-binding factor, 35 kDa). Mutations that alter in vitro binding of either MEF-2 or ATF35 to this site diminish promoter function in vivo. Functional synergism between factors binding the CCAC and A/T elements is sensitive to subtle mutations in the TATA sequence, recapitulating the unusual preference for specific TATA variants exhibited by the native myoglobin promoter. These results provide new insights into mechanisms that underlie the distinctive pattern of myoglobin gene regulation in mammalian muscle development and lay a foundation for further studies to elucidate general principles of transcriptional control of complex mammalian promoters through combinatorial actions of heterologous transcription factors.

Original languageEnglish (US)
Pages (from-to)1870-1878
Number of pages9
JournalMolecular and cellular biology
Volume15
Issue number4
DOIs
StatePublished - Apr 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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