期刊
GENES & DEVELOPMENT
卷 24, 期 4, 页码 327-332出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1882610
关键词
Gene regulation; epigenetics; chromatin; histone demethylation; cancer
资金
- California Institute for Regenerative Medicine [RN1-00529-1]
- National Cancer Institute [R01-CA118487, R01-CA118750]
- American Cancer Society [RSG 07-084-01-MGO]
- Medical Research Council [G0600127] Funding Source: researchfish
- MRC [G0600127] Funding Source: UKRI
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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