Histone Deacetylase 3 Modulates Tbx5 Activity to Regulate Early Cardiogenesis
Authors
Lewandowski, Sara L.Janardhan, Harish P.
Smee, Kevin M.
Bachman, Marcos
Sun, Zheng
Lazar, Mitchell A.
Trivedi, Chinmay M.
Student Authors
Sara L. Lewandowski; Harish P. Janardhan; Kevin M. Smee; Marcos BachmanUMass Chan Affiliations
School of MedicineDepartment of Medicine, Division of Cardiovascular Medicine
Document Type
Journal ArticlePublication Date
2014-03-05Keywords
Histone deacetylaseprogenitor cells
Holt-Oram Syndrome
T-box gene
heart development
Cardiology
Cell Biology
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Developmental Biology
Laboratory and Basic Science Research
Molecular Genetics
Pediatrics
Metadata
Show full item recordAbstract
Congenital heart defects often result from improper differentiation of cardiac progenitor cells. Although transcription factors involved in cardiac progenitor cell differentiation have been described, the associated chromatin modifiers in this process remain largely unknown. Here we show that mouse embryos lacking the chromatin-modifying enzyme histone deacetylase 3 (Hdac3) in cardiac progenitor cells exhibit precocious cardiomyocyte differentiation, severe cardiac developmental defects, upregulation of Tbx5 target genes and embryonic lethality. Hdac3 physically interacts with Tbx5 and modulates its acetylation to repress Tbx5-dependent activation of cardiomyocyte lineage-specific genes. These findings reveal that Hdac3 plays a critical role in cardiac progenitor cells to regulate early cardiogenesis.Source
Lewandowski SL, Janardhan HP, Smee KM, Bachman M, Sun Z, Lazar MA, Trivedi CM. Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis. Hum Mol Genet. 2014 Mar 5.
DOI
10.1093/hmg/ddu093Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33321PubMed ID
24565863Related Resources
ae974a485f413a2113503eed53cd6c53
10.1093/hmg/ddu093