UTX, a histone H3-lysine 27 demethylase, acts as a critical switch to activate the cardiac developmental program

Dev Cell. 2012 Jan 17;22(1):25-37. doi: 10.1016/j.devcel.2011.11.009. Epub 2011 Dec 20.


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.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Chromatin / genetics*
  • Chromatin Immunoprecipitation
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Enhancer Elements, Genetic / genetics*
  • Flow Cytometry
  • Genes, Lethal
  • Heart / embryology
  • Heart / growth & development*
  • Histone Demethylases
  • Histones / genetics
  • Histones / metabolism*
  • Immunoenzyme Techniques
  • Luciferases / metabolism
  • Methylation
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Chromatin
  • Histones
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Luciferases
  • Histone Demethylases
  • Utx protein, mouse
  • Smarca4 protein, mouse
  • DNA Helicases