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skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration.


Cardiac and skeletal muscle development and maintenance require complex interactions between DNA-binding proteins and chromatin remodeling factors. We previously reported that Smyd1, a muscle-restricted histone methyltransferase, is essential for cardiogenesis and functions with a network of cardiac regulatory proteins. Here we show that the muscle-specific transcription factor skNAC is the major binding partner for Smyd1 in the developing heart. Targeted deletion of skNAC in mice resulted in partial embryonic lethality by embryonic day 12.5, with ventricular hypoplasia and decreased cardiomyocyte proliferation that were similar but less severe than in Smyd1 mutants. Expression of Irx4, a ventricle-specific transcription factor down-regulated in hearts lacking Smyd1, also depended on the presence of skNAC. Viable skNAC(-/-) adult mice had reduced postnatal skeletal muscle growth and impaired regenerative capacity after cardiotoxin-induced injury. Satellite cells isolated from skNAC(-/-) mice had impaired survival compared with wild-type littermate satellite cells. Our results indicate that skNAC plays a critical role in ventricular cardiomyocyte expansion and regulates postnatal skeletal muscle growth and regeneration in mice.

Pubmed ID: 21071677


  • Park CY
  • Pierce SA
  • von Drehle M
  • Ivey KN
  • Morgan JA
  • Blau HM
  • Srivastava D


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

November 30, 2010

Associated Grants

  • Agency: NCRR NIH HHS, Id: C06 RR018928
  • Agency: NIA NIH HHS, Id: R01 AG009521
  • Agency: NIA NIH HHS, Id: R01 AG020961
  • Agency: NHLBI NIH HHS, Id: U01 HL100397

Mesh Terms

  • Animals
  • Animals, Newborn
  • Body Patterning
  • Cell Proliferation
  • DNA-Binding Proteins
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Heart
  • Heart Ventricles
  • Mice
  • Molecular Chaperones
  • Muscle Development
  • Muscle Fibers, Skeletal
  • Muscle Proteins
  • Muscle, Skeletal
  • Myocardium
  • Myocytes, Cardiac
  • Organ Specificity
  • Organogenesis
  • Protein Binding
  • Regeneration
  • Transcription Factors