Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function

Hum Mol Genet. 2012 May 15;21(10):2194-204. doi: 10.1093/hmg/dds034. Epub 2012 Feb 10.


The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number (http://www.ncbi.nlm.nih.gov/geo): GSE30943.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / pathology
  • Cardiomyopathies / physiopathology
  • Chromatin Immunoprecipitation
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Mice
  • Mice, Knockout
  • Myocardial Contraction
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism*
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • T-Box Domain Proteins
  • Tbx20 protein, mouse
  • Transcription Factors

Associated data

  • GEO/GSE30943