| Literature DB >> 27229140 |
Dong Fang1, Haiyun Gan1, Jeong-Heon Lee2, Jing Han1, Zhiquan Wang1, Scott M Riester3, Long Jin3, Jianji Chen4, Hui Zhou1, Jinglong Wang5, Honglian Zhang1, Na Yang6, Elizabeth W Bradley3, Thai H Ho7, Brian P Rubin8, Julia A Bridge9, Stephen N Thibodeau10, Tamas Ordog11, Yue Chen4, Andre J van Wijnen12, Andre M Oliveira13, Rui-Ming Xu5, Jennifer J Westendorf12, Zhiguo Zhang14.
Abstract
More than 90% of chondroblastomas contain a heterozygous mutation replacing lysine-36 with methionine-36 (K36M) in the histone H3 variant H3.3. Here we show that H3K36 methylation is reduced globally in human chondroblastomas and in chondrocytes harboring the same genetic mutation, due to inhibition of at least two H3K36 methyltransferases, MMSET and SETD2, by the H3.3K36M mutant proteins. Genes with altered expression as well as H3K36 di- and trimethylation in H3.3K36M cells are enriched in cancer pathways. In addition, H3.3K36M chondrocytes exhibit several hallmarks of cancer cells, including increased ability to form colonies, resistance to apoptosis, and defects in differentiation. Thus, H3.3K36M proteins reprogram the H3K36 methylation landscape and contribute to tumorigenesis, in part through altering the expression of cancer-associated genes.Entities:
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Year: 2016 PMID： 27229140 PMCID： PMC5460624 DOI： 10.1126/science.aae0065
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728