Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different diseases.The H3K27M and H3K36M mutant histones exert dominant-negative effects on methyla...Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different diseases.The H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wildtype histone protein in pediatric brain cancers2–4 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).展开更多
Dear Editor,Histones are essential proteins in compacting genomic DNA and regulating gene expression.Previous studies on histone H3 oncohistones in pediatric brain cancers1,2 and chondroblastoma3,documented the transc...Dear Editor,Histones are essential proteins in compacting genomic DNA and regulating gene expression.Previous studies on histone H3 oncohistones in pediatric brain cancers1,2 and chondroblastoma3,documented the transcriptomic reprogramming through the alterations of histone modifications.We recently reported the identification of a novel cancer associated mutation,the H2BG53-to-D in pancreatic ductal adenocarcinoma(PDAC)4.We showed that the H2BG53D mutation weakens the interaction between nucleosomal DNA and histone octamer,subsequently enhances transcription in vitro.We further showed that cells expressing the G53D mutant H2B acquired oncogenic phenotypes in our CRISPRCas9 knock-in model.However,the mechanism by which H2BG53D mutation promotes PDAC remains unknown.展开更多
基金supported by grants from Research Grants Council Hong Kong[Project Nos.17101814,21100615,11102118,11101919(to K.M.C.),11102317(to X.W.),26100214(to T.I.)and C7007-17GF(to M.S.Y.H.,K.M.C.,and T.I.)]the Shenzhen Science and Technology Fund Program Project Nos.JCYJ20170818104203065,JCYJ20180307124019360(to K.M.C.)and JCYJ20170307091256048(to X.W.)+1 种基金National Natural Science Foundation of China[Project No.81802384(to X.W.)]supported by the Hong Kong Epigenomics Project of the EpiHK(to K.M.C.)and grants from the National Cancer Institute,National Institute of Health[CA72851,CA187956,CA202797,CA214254(to A.G.)].
文摘Dear Editor,Recent studies from us and others have deciphered the clinical relevance of a variety of oncohistones1 in different diseases.The H3K27M and H3K36M mutant histones exert dominant-negative effects on methylation levels of histone H3K27 and H3K36 on wildtype histone protein in pediatric brain cancers2–4 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).
基金supported by grants from Research Grants Council Hong Kong[Project No.17101814,21100615,11102118,11101919(K.M.C.),11102317(X.W.),and C7007-17GF(K.M.C.)]the Shenzhen Science and Technology Fund Program Project No.JCYJ20170818104203065,JCYJ20180307124019360(K.M.C.),JCYJ20170307091256048(X.W.)National Natural Science Foundation of China[Project No.81802384(X.W.)].This work was also supported by the Hong Kong Epigenomics Project of the EpiHK(K.M.C.).
文摘Dear Editor,Histones are essential proteins in compacting genomic DNA and regulating gene expression.Previous studies on histone H3 oncohistones in pediatric brain cancers1,2 and chondroblastoma3,documented the transcriptomic reprogramming through the alterations of histone modifications.We recently reported the identification of a novel cancer associated mutation,the H2BG53-to-D in pancreatic ductal adenocarcinoma(PDAC)4.We showed that the H2BG53D mutation weakens the interaction between nucleosomal DNA and histone octamer,subsequently enhances transcription in vitro.We further showed that cells expressing the G53D mutant H2B acquired oncogenic phenotypes in our CRISPRCas9 knock-in model.However,the mechanism by which H2BG53D mutation promotes PDAC remains unknown.
