CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice

Academic Article


  • Haploinsufficiency for CHD7, an ATP-dependent nucleosome remodeling factor, is the leading cause of CHARGE syndrome. While congenital heart defects (CHDs) are major clinical features of CHARGE syndrome, affecting >75%of patients, itremains unclear whether CHD7 can directly regulate cardiogenic genesin embryos. Our complementary yeast two-hybrid and biochemical assays reveal that CHD7 is a novel interaction partner of canonical BMP signaling pathway nuclear mediators, SMAD1/5/8, in the embryonic heart. Moreover, CHD7 associates in a BMP-dependent manner with the enhancers of a critical cardiac transcription factor, Nkx2.5, that contain functional SMAD1-binding elements. Both the active epigenetic signature of Nkx2.5 regulatory elements and its proper expression in cardiomyocytes require CHD7. Finally, inactivation of Chd7 in mice impairs multiple BMP signaling-regulated cardiogenic processes. Our results thus support the model that CHD7 is recruited by SMAD1/5/8 to the enhancers of BMP-targeted cardiogenic genes to epigenetically regulate their expression. Impaired BMP activities in embryonic hearts may thus have amajor contribution to CHDs in CHARGE syndrome. © The Author 2013. Published by Oxford University Press. All rights reserved.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Liu Y; Harmelink C; Peng Y; Chen Y; Wang Q; Jiao K
  • Start Page

  • 2145
  • End Page

  • 2156
  • Volume

  • 23
  • Issue

  • 8