Codependent activators direct myoblast-specific MyoD transcription. Academic Article uri icon

Overview

abstract

  • Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription.

publication date

  • October 1, 2008

Research

keywords

  • Forkhead Transcription Factors
  • MyoD Protein
  • Paired Box Transcription Factors
  • Trans-Activators
  • Transcription, Genetic

Identity

PubMed Central ID

  • PMC2614327

Scopus Document Identifier

  • 53249095869

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2008.08.018

PubMed ID

  • 18854138

Additional Document Info

volume

  • 15

issue

  • 4