Title | The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Waldron, L, Steimle, JD, Greco, TM, Gomez, NC, Dorr, KM, Kweon, J, Temple, B, Yang, XHolly, Wilczewski, CM, Davis, IJ, Cristea, IM, Moskowitz, IP, Conlon, FL |
Journal | Dev Cell |
Volume | 36 |
Issue | 3 |
Pagination | 262-75 |
Date Published | 2016 Feb 08 |
ISSN | 1878-1551 |
Keywords | Animals, Chromatin Assembly and Disassembly, Gene Expression Regulation, Developmental, Heart, Humans, Mice, Transgenic, Myocardium, Organogenesis, T-Box Domain Proteins, Transcription, Genetic |
Abstract | <p>Human mutations in the cardiac transcription factor gene TBX5 cause congenital heart disease (CHD), although the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the nucleosome remodeling and deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart. CHD mis-sense mutations that disrupt the TBX5-NuRD interaction cause depression of a subset of repressed genes. Furthermore, the TBX5-NuRD interaction is required for heart development. Phylogenetic analysis showed that the TBX5-NuRD interaction domain evolved during early diversification of vertebrates, simultaneous with the evolution of cardiac septation. Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD.</p> |
DOI | 10.1016/j.devcel.2016.01.009 |
Alternate Journal | Dev Cell |
PubMed ID | 26859351 |
PubMed Central ID | PMC4920128 |
Grant List | NIH/NIGMS R01 GM114141 / / PHS HHS / United States R21CA167305 / CA / NCI NIH HHS / United States R21 CA167305 / CA / NCI NIH HHS / United States R01 HL112618 / HL / NHLBI NIH HHS / United States T32 GM007092 / GM / NIGMS NIH HHS / United States 11PRE6110002 / AHA / American Heart Association-American Stroke Association / United States R01 HL124836 / HL / NHLBI NIH HHS / United States HL127640 / HL / NHLBI NIH HHS / United States R01HL124836 / HL / NHLBI NIH HHS / United States NIH RO1HL112618 / HL / NHLBI NIH HHS / United States P30 CA016086 / CA / NCI NIH HHS / United States S10 OD018495 / OD / NIH HHS / United States T32 HL007381 / HL / NHLBI NIH HHS / United States R01 GM114141 / GM / NIGMS NIH HHS / United States R01 HL127640 / HL / NHLBI NIH HHS / United States R01 HL092153 / HL / NHLBI NIH HHS / United States 1S10OD018495-01 / OD / NIH HHS / United States NIH T32 GM007183 / GM / NIGMS NIH HHS / United States 5T32 GM007092 / GM / NIGMS NIH HHS / United States T32 HL069768 / HL / NHLBI NIH HHS / United States T32 GM007183 / GM / NIGMS NIH HHS / United States P40 OD010997 / OD / NIH HHS / United States |