Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium

Rhonda S Bassel-Duby, Christian M. Grohe, Michael E Jessen, William J. Parsons, James A Richardson, Robert Chao, Jayson Grayson, W Steves Ring, R. Sanders Williams

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

To define sequence elements required for myoglobin gene transcription in the intact heart, we examined the expression of a reporter gene under the control of a 380-bp upstream segment (-373 to +7) from the human myoglobin gene in transgenic mouse embryos and after gene transfer into left ventricular myocardium of adult rats. This proximal upstream region was sufficient to direct expression of luciferase selectively in cardiac and skeletal muscle of mouse embryos and to recapitulate the pattern of expression of the endogenous mouse myoglobin gene. This same upstream region was transcriptionally active after injection of plasmid DNA into the left ventricular wall of adult rats. Point mutations within two evolutionarily conserved sequence elements - a cytosine-rich (CCAC-box) motif and an A+T-rich (A/T) motif - severely impaired transcription within the intact heart. Nuclear extracts from neonatal cardiomyocytes contain protein factors that bind to each of these elements in a sequence-specific manner. We conclude that combinatorial interactions between the cognate DNA binding factors that recognize these motifs are necessary for transcriptional activity of the myoglobin upstream region in cardiac muscle.

Original languageEnglish (US)
Pages (from-to)360-366
Number of pages7
JournalCirculation research
Volume73
Issue number2
StatePublished - Aug 1993

Keywords

  • Gene transfer
  • Human myoglobin gene

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

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