UTX, a Histone H3-Lysine 27 Demethylase, Acts as a Critical Switch to Activate the Cardiac Developmental Program

Seunghee Lee, Jae W. Lee, Soo Kyung Lee

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

The removal of histone H3 lysine27 (H3K27) trimethylation mark is important for the robust induction of many cell type-specific genes during differentiation. Here we show that UTX, a H3K27 demethylase, acts as a critical switch to promote a cardiac-specific gene program. UTX-deficient ESCs failed to develop heart-like rhythmic contractions under a cardiac differentiation condition. UTX-deficient mice show severe defects in heart development and embryonic lethality. We found that UTX is recruited to cardiac-specific enhancers by associating with core cardiac transcription factors and demethylates H3K27 residues in cardiac genes. In addition, UTX facilitates the recruitment of Brg1 to the cardiac-specific enhancers. Together, our data reveal key roles for UTX in a timely transition from poised to active chromatin in cardiac genes during heart development and a fundamental mechanism by which a H3K27 demethylase triggers tissue-specific chromatin changes.

Original languageEnglish (US)
Pages (from-to)25-37
Number of pages13
JournalDevelopmental Cell
Volume22
Issue number1
DOIs
StatePublished - Jan 17 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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