气候变化领域集成服务门户(CCPortal): Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation

CCPortal

DOI	10.1073/pnas.2021795118
	Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation
	Rajagopalan K.N.; Chen X.; Weinberg D.N.; Chen H.; Majewski J.; Allis C.D.; Lu C.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	Hotspot histone H3 mutations have emerged as drivers of oncogenesis in cancers of multiple lineages. Specifically, H3 lysine 36 to methionine (H3K36M) mutations are recurrently identified in chondroblastomas, undifferentiated sarcomas, and head and neck cancers. While the mutation reduces global levels of both H3K36 dimethylation (H3K36me2) and trimethylation (H3K36me3) by dominantly inhibiting their respective specific methyltransferases, the relative contribution of these methylation states to the chromatin and phenotypic changes associated with H3K36M remains unclear. Here, we specifically deplete H3K36me2 or H3K36me3 in mesenchymal cells, using CRISPR-Cas9 to separately knock out the corresponding methyltransferases NSD1/2 or SETD2. By profiling and comparing the epigenomic and transcriptomic landscapes of these cells with cells expressing the H3.3K36M oncohistone, we find that the loss of H3K36me2 could largely recapitulate H3.3K36M's effect on redistribution of H3K27 trimethylation (H3K27me3) and gene expression. Consistently, knockout of Nsd1/ 2, but not Setd2, phenocopies the differentiation blockade and hypersensitivity to the DNA-hypomethylating agent induced by H3K36M. Together, our results support a functional divergence between H3K36me2 and H3K36me3 and their nonredundant roles in H3K36M-driven oncogenesis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Cancer; Chromatin and epigenomics; H3K36 methylation; NSD; Oncohistone
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180456
作者单位	Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University, Irving Medical Center, New York, NY 10032, United States; Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, NY 10065, United States; Department of Genetics and Development, Columbia University, Irving Medical Center, New York, NY 10032, United States; Herbert Irving Comprehensive Cancer Center, Columbia University, Irving Medical Center, New York, NY 10032, United States; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada
推荐引用方式 GB/T 7714	Rajagopalan K.N.,Chen X.,Weinberg D.N.,et al. Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation[J],2021,118(9).
APA	Rajagopalan K.N..,Chen X..,Weinberg D.N..,Chen H..,Majewski J..,...&Lu C..(2021).Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Rajagopalan K.N.,et al."Depletion of H3K36me2 recapitulates epigenomic and phenotypic changes induced by the H3.3K36M oncohistone mutation".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).