Chromatin modifications remodel cardiac gene expression

Prabhu Mathiyalagan, Samuel T Keating, Xiao-Jun Du, Assam El-Osta

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Signalling and transcriptional control involve precise programmes of gene activation and suppression necessary for cardiovascular physiology. Deep sequencing of DNA-bound transcription factors reveals a remarkable complexity of co-activators or co-repressors that serve to alter chromatin modification and regulate gene expression. The regulated complexes characterized by genome-wide mapping implicate the recruitment and exchange of proteins with specific enzymatic activities that include roles for histone acetylation and methylation in key developmental programmes of the heart. As for transcriptional changes in response to pathological stress, co-regulatory complexes are also differentially utilized to regulate genes in cardiac disease. Members of the histone deacetylase (HDAC) family catalyse the removal of acetyl groups from proteins whose pharmacological inhibition has profound effects preventing heart failure. HDACs interact with a complex co-regulatory network of transcription factors, chromatin-remodelling complexes, and specific histone modifiers to regulate gene expression in the heart. For example, the histone methyltransferase (HMT), enhancer of zeste homolog 2 (Ezh2), is regulated by HDAC inhibition and associated with pathological cardiac hypertrophy. The challenge now is to target the activity of enzymes involved in protein modification to prevent or reverse the expression of genes implicated with cardiac hypertrophy. In this review, we discuss the role of HDACs and HMTs with a focus on chromatin modification and gene function as well as the clinical treatment of heart failure.
Original languageEnglish
Pages (from-to)7-16
Number of pages10
JournalCardiovascular Research
Volume103
Issue number1
DOIs
Publication statusPublished - 2014

Keywords

  • Cardiac hypertrophy
  • Gene regulation
  • Histone acetylation
  • Histone methylation
  • Chromatin remodelling

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