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Here, we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and contributes to tumorigenesis in part by locally enhancing H3K27me3, and hence silencing of tumor suppressor genes.<\/jats:p>","DOI":"10.7554\/elife.36696","type":"journal-article","created":{"date-parts":[[2018,6,22]],"date-time":"2018-06-22T08:00:34Z","timestamp":1529654434000},"source":"Crossref","is-referenced-by-count":93,"title":["H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-5224","authenticated-orcid":true,"given":"Dong","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Department of Genetics and Development, Institute for Cancer Genetics, Irving Cancer Research Center, Columbia University, New York, United 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