Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding

Tushar Chakraborty, Thomas J. Brennan, Li Li, Diane Edmondson, Eric N. Olson

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Myogenin is a muscle-specific transcription factor that can activate myogenesis; it belongs to a family of transcription factors that share homology within a basic region and an adjacent helix-loop-helix (HLH) motif. Although myogenin alone binds DNA inefficiently, in the presence of the widely expressed HLH proteins E12 and E47 (encoded by the E2A gene), it forms heterooligomers that bind with high affinity to a DNA sequence known as a ΚE-2 site. In contrast, E47 and to a lesser extent E12 are both able to bind the ΚE-2 site relatively efficiently as homooligomers. To define the relative contributions of the basic regions of myogenin and E12 to DNA binding and muscle-specific gene activation, we created chimeras of the two proteins by swapping their basic regions. We showed that myogenin's weak affinity for the ΚE-2 site is attributable to inefficient homooligomerization and that the myogenin basic domain alone can mediate high-affinity DNA binding when placed in E12. Within a heterooligomeric complex, two basic regions were required to form a high-affinity DNA-binding domain. Basic-domain mutants of myogenin or E2A gene products that cannot bind DNA retained the ability to oligomerize and could abolish DNA binding of the wild-type proteins in vitro. These myogenin and E2A mutants also acted as trans-dominant inhibitors of muscle-specific gene activation in vivo. These findings support the notion that muscle-specific gene activation requires oligomerization between myogenin and E2A gene products and that E2A gene products play an important role in myogenesis by enhancing the DNA-binding activity of myogenin, as well as other myogenic HLH proteins.

Original languageEnglish (US)
Pages (from-to)3633-3641
Number of pages9
JournalMolecular and Cellular Biology
Volume11
Issue number7
StatePublished - Jul 1991

Fingerprint

Myogenin
DNA
Transcription Factor 3
Transcriptional Activation
Muscles
Muscle Development
Genes
Helix-Loop-Helix Motifs
Transcription Factors
DNA-Binding Proteins
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding. / Chakraborty, Tushar; Brennan, Thomas J.; Li, Li; Edmondson, Diane; Olson, Eric N.

In: Molecular and Cellular Biology, Vol. 11, No. 7, 07.1991, p. 3633-3641.

Research output: Contribution to journalArticle

Chakraborty, Tushar ; Brennan, Thomas J. ; Li, Li ; Edmondson, Diane ; Olson, Eric N. / Inefficient homooligomerization contributes to the dependence of myogenin on E2A products for efficient DNA binding. In: Molecular and Cellular Biology. 1991 ; Vol. 11, No. 7. pp. 3633-3641.
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