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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bassel-Duby, R; Grohe, CM; Jessen, ME; Parsons, WJ; Richardson, JA; Chao, R; Grayson, J; Ring, WS; Williams, RS

Published Date

  • August 1993

Published In

Volume / Issue

  • 73 / 2

Start / End Page

  • 360 - 366

PubMed ID

  • 8330378

Pubmed Central ID

  • 8330378

International Standard Serial Number (ISSN)

  • 0009-7330

Digital Object Identifier (DOI)

  • 10.1161/01.res.73.2.360

Language

  • eng

Conference Location

  • United States