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 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.
