Myocardin-related transcription factors are required for cardiac development and function

Mayssa H. Mokalled, Kelli J. Carroll, Bercin K. Cenik, Beibei Chen, Ning Liu, Eric N. Olson, Rhonda Bassel-Duby

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks.

Original languageEnglish (US)
Pages (from-to)109-116
Number of pages8
JournalDevelopmental Biology
Volume406
Issue number2
DOIs
StatePublished - Oct 15 2015

Keywords

  • Cardiac morphogenesis
  • Cytoskeletal dynamics
  • Heart function
  • MRTF-A/MKL1
  • MRTF-B/MKL2
  • Sarcomere arrangement

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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