title: Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis.
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.
authors.affiliation: Cardiovascular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Lewandowski
authors.affiliation: Cardiovascular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Harish P
authors.initials: HP
authors.lastname: Janardhan
authors.affiliation: Cardiovascular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Smee
authors.affiliation: Cardiovascular Medicine and.
authors.forename: Marcos
authors.initials: M
authors.lastname: Bachman
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, Department of Medicine and The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
authors.affiliation: Cardiovascular Medicine and Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA, chinmay.trivedi@umassmed.edu.
authors.forename: Chinmay M
authors.initials: CM
authors.lastname: Trivedi
mesh_terms: D000107:Acetylation; D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D057809:HEK293 Cells; D006321:Heart / Q000196:embryology* / Q000254:growth & development / Q000503:physiopathology; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D020825:T-Box Domain Proteins; D000099186:Histone Deacetylase 3; C103172:T-box transcription factor 5