Title
Histone Deacetylase 3 Modulates Tbx5 Activity to Regulate Early Cardiogenesis
Academic Program
Translational Science
UMMS Affiliation
Department of Medicine, Division of Cardiovascular Medicine; School of Medicine
Publication Date
2014-03-05
Document Type
Article
Disciplines
Cardiology | Cell Biology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Developmental Biology | Laboratory and Basic Science Research | Molecular Genetics | Pediatrics
Abstract
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.
Keywords
Histone deacetylase, progenitor cells, Holt-Oram Syndrome, T-box gene, heart development
DOI of Published Version
10.1093/hmg/ddu093
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.
Journal/Book/Conference Title
Human Molecular Genetics
Related Resources
PubMed ID
24565863
Repository Citation
Lewandowski SL, Janardhan HP, Smee KM, Bachman M, Sun Z, Lazar MA, Trivedi CM. (2014). Histone Deacetylase 3 Modulates Tbx5 Activity to Regulate Early Cardiogenesis. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1093/hmg/ddu093. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1849