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

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

Author information

1
Pediatric Neuroscience Research Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.

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.

PMID:
22192413
PMCID:
PMC4111644
DOI:
10.1016/j.devcel.2011.11.009
[Indexed for MEDLINE]
Free PMC Article

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