| First Author | Liu Y | Year | 2014 |
| Journal | Hum Mol Genet | Volume | 23 |
| Issue | 8 | Pages | 2145-56 |
| PubMed ID | 24293546 | Mgi Jnum | J:207089 |
| Mgi Id | MGI:5554454 | Doi | 10.1093/hmg/ddt610 |
| Citation | Liu Y, et al. (2014) CHD7 interacts with BMP R-SMADs to epigenetically regulate cardiogenesis in mice. Hum Mol Genet 23(8):2145-56 |
| abstractText | 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, it remains unclear whether CHD7 can directly regulate cardiogenic genes in 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 a major contribution to CHDs in CHARGE syndrome. |
