Cancer-associated histone mutation H2BG53D disrupts DNA–histone octamer interaction and promotes oncogenic phenotypes
Year: 2020
Type: article
Abstract: Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones 1 in different diseases. The H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wild-type histone protein in pediatric brain cancers 2 , 3 , 4 and chondroblastoma, 5 , 6 respectively. In contrast to H3K27M and H3K36M that act in trans to cause global reduction of methylation at the respective residues, the H3G34 mutations, including H3G34V/R and H3G34W/L found in pediatric high-grade glioma and giant cell tumor of the bone, affect the H3K36 methylation in cis and alter the H3K36 methylation on the nucleosome containing the H3G34 mutation(s). In addition to histone H3, two recent reports revealed another class of oncogenic mutation in histone H2B. 7 , 8 The glutamic acid at position 76 of H2B was found to be replaced by lysine in multiple cancers, including breast and lung carcinomas. Cells expressing the H2BE76K mutation acquired oncogenic phenotypes as a result of aberrant gene expression associated with cancer pathways, an effect possibly due to the destabilization of the histone octamer by H2BE76K. Together, these studies indicated that missense mutations in histone genes impact gene expression and play a vital role in driving tumorigenesis by distinct mechanisms.
Authors: Yi Ching Esther Wan, Tsz Chui Sophia Leung, Dongbo Ding, Xulun Sun, Jiaxian Liu, Lina Zhu, Tze Zhen Evangeline Kang, Du Yang, Yuchen Zhang, Jitian Zhang, Chengmin Qian, Michael Shing Yan Huen, Qing Li, Maggie Zi Ying Chow, Zongli Zheng, Junhong Han, Ajay Goel, Xin Wang, Toyotaka Ishibashi, Kui Ming Chan
Institutions: City University of Hong Kong, City University of Hong Kong, Shenzhen Research Institute, Hong Kong University of Science and Technology, Peking University, Center for Life Sciences, State Key Laboratory of Protein and Plant Gene Research, University of Hong Kong, Karolinska Institutet, Ming Wai Lau Centre for Reparative Medicine, Sichuan University, State Key Laboratory of Biotherapy, City Of Hope National Medical Center, City of Hope, Beckman Research Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,680
Funders: U.S. Department of Health and Human Services, City University of Hong Kong, Beckman Research Institute, City of Hope, Comprehensive Cancer Center, City of Hope, National Natural Science Foundation of China, Research Grants Council, University Grants Committee, University of Hong Kong, Karolinska Institutet, Sichuan University, Peking University, Science, Technology and Innovation Commission of Shenzhen Municipality, National Institutes of Health, Shenzhen Research Institute, City University of Hong Kong, West China Hospital, Sichuan University, National Cancer Institute
Awards: Elucidating the role of chromatin dynamics during spermatogenesis and its impact on transcription at the single-molecule level., G2224762734, G251590960, G2686223150, Consensus molecular subtyping of pancreatic ductal adenocarcinoma and tumor-intrinsic regulatory network inference from deconvolved gene expression profiles, G3411000325, Elucidating the functional significance of the Lrwd1-ORC interaction, G3881707981, G4089707383, G4144402113, Elucidate the biological significance of Histone H2BG54D mutation in pancreatic cancer, Deciphering the molecular mechanisms of H2BE76K mutation in cancer, G4300560175, 基于材料尺寸效应的MgO混凝土梯度依赖损伤塑性耦合机理研究, MicroRNA Biomarkers for Determining Treatment Response in Colorectal Cancer, G6116462610, Functional analysis of the role of Mcm3 in epigenetic gene silencing, G6681643532, Noncoding RNA Biomarkers for Noninvasive and Early Detection of Pancreatic Cancer, G7049232908, G7209363012, G7384640205, G7911394405, G7927873919, G8377572790, Aspirin and Cancer Prevention in Lynch Syndrome: From Cell to Population Data
OpenAlex ID: W3010569736