The histone demethylase UTX enables RB-dependent cell fate control
- Jordon K. Wang1,
- Miao-Chih Tsai1,
- Gino Poulin2,
- Adam S. Adler1,
- Shuzhen Chen3,4,
- Helen Liu1,
- Yang Shi3,4 and
- Howard Y. Chang1,5
- 1Howard Hughes Medical Institute and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
- 2Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom;
- 3Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4Division of Newborn Medicine, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts 02115, USA
Abstract
Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis of UTX and associated histone modifications reveals distinct classes of UTX target genes, including genes encoding Retinoblastoma (RB)-binding proteins. UTX removes H3K27me3 and maintains expression of several RB-binding proteins, enabling cell cycle arrest. Genetic interactions in mammalian cells and Caenorhabditis elegans show that UTX regulates cell fates via RB-dependent pathways. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control.
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Footnotes
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↵5 Corresponding author.
E-MAIL howchang{at}stanford.edu; FAX (650) 723-8762.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1882610.
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Supplemental material is available at http://www.genesdev.org.
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- Received November 5, 2009.
- Accepted December 15, 2009.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
