The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis

Richard M. Cripps, Brian L. Black, Bin Zhao, Ching Ling Lien, Robert A. Schulz, Eric N. Olson

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

MEF2 is a MADS-box transcription factor required for muscle development in Drosophila. Here, we show that the bHLH transcription factor Twist directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcriptional start site. Within this element, a single evolutionarily conserved E box is essential for enhancer activity. Twist protein can bind to this E box to activate Mef2 transcription, and ectopic expression of twist results in ectopic activation of the wild-type 175-bp enhancer. By use of a temperature- sensitive mutant of twist, we show that activation of Mef2 transcription via this enhancer by Twist is required for normal adult muscle development, and reduction in Twist function results in phenotypes similar to those observed previously in Mef2 mutant adults. The 175-bp enhancer is also active in the embryonic mesoderm, indicating that this enhancer functions at multiple times during development, and its function is dependent on the same conserved E box. In embryos, a reduction in Twist function also strongly reduced Mef2 expression. These findings define a novel transcriptional pathway required for skeletal muscle development and identify Twist as an essential and direct regulator of Mef2 expression in the somatic mesoderm.

Original languageEnglish (US)
Pages (from-to)422-434
Number of pages13
JournalGenes and Development
Volume12
Issue number3
DOIs
StatePublished - Feb 1 1998

Keywords

  • Adepithelial cells
  • Drosophila
  • Imaginal discs
  • MEF2
  • Muscle development
  • Twist

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis'. Together they form a unique fingerprint.

  • Cite this