Title

Histone Deacetylase 3 Modulates Tbx5 Activity to Regulate Early Cardiogenesis

Student Author(s)

Sara L. Lewandowski; Harish P. Janardhan; Kevin M. Smee; Marcos Bachman

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

Link to article in PubMed

PubMed ID

24565863

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