Skip to main content
Open Access Publications from the University of California

Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites.

  • Author(s): Anderson, Courtney M
  • Hu, Jianxin
  • Thomas, Reuben
  • Gainous, T Blair
  • Celona, Barbara
  • Sinha, Tanvi
  • Dickel, Diane E
  • Heidt, Analeah B
  • Xu, Shan-Mei
  • Bruneau, Benoit G
  • Pollard, Katherine S
  • Pennacchio, Len A
  • Black, Brian L
  • et al.

Published Web Location
No data is associated with this publication.

Enhancers frequently contain multiple binding sites for the same transcription factor. These homotypic binding sites often exhibit synergy, whereby the transcriptional output from two or more binding sites is greater than the sum of the contributions of the individual binding sites alone. Although this phenomenon is frequently observed, the mechanistic basis for homotypic binding site synergy is poorly understood. Here, we identify a bona fide cardiac-specific Prkaa2 enhancer that is synergistically activated by homotypic MEF2 binding sites. We show that two MEF2 sites in the enhancer function cooperatively due to bridging of the MEF2C-bound sites by the SAP domain-containing co-activator protein myocardin, and we show that paired sites buffer the enhancer from integration site-dependent effects on transcription in vivo Paired MEF2 sites are prevalent in cardiac enhancers, suggesting that this might be a common mechanism underlying synergy in the control of cardiac gene expression in vivo.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Item not freely available? Link broken?
Report a problem accessing this item