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典型文献
Involvement of PGC7 and UHRF1 in the regulation of DNA methylation of the IG-DMR in the imprinted Dlk1-Dio3 locus
文献摘要:
The gene dosage at the imprinted Dlk1-Dio3 locus is critical for cell growth and development.A relatively high gene expression within the Dlk1-Dio3 region,especially the active expression of Gtl2,has been identified as the only reliable marker for cell pluripotency.The DNA methylation state of the IG-DNA methylated regions(DMR),which is located upstream of the Gtl2 gene,dominantly contributes to the control of gene expression in the Dlk1-Dio3 locus.However,the precise mechanism underlying the regulation of DNA methylation in the IG-DMR remains largely unknown.Here,we use the F9 embryonal carcinoma cell line,a low pluripotent cell model,to identify the me-chanism responsible for DNA methylation in the IG-DMR,and find that the interaction of PGC7 with UHRF1 is involved in maintaining DNA methylation and inducing DNA hypermethylation in the IG-DMR region.PGC7 and UHRF1 cooperatively bind in the IG-DMR to regulate the methylation of DNA and histones in this imprinted region.PGC7 promotes the recruitment of DNMT1 by UHRF1 to maintain DNA methylation in the IG-DMR locus.The interaction between PGC7 and UHRF1 strengthens their binding to H3K9me3 and leads to further enrichment of H3K9me3 in the IG-DMR by recruiting the specific histone methyltransferase SETDB1.Consequently,the abundance of H3K9me3 promotes DNMT3A to bind to the IG-DMR and increases DNA methylation level in this region.In summary,we propose a new mechanism of DNA methylation regulation in the IG-DMR locus and provide further insight into the understanding of the difference in Gtl2 expression levels between high and low pluripotent cells.
文献关键词:
作者姓名:
Mengying Yu;Yingxiang Liu;Zhuo Han;Wei Du;Bingxue Chen;Lei Zhang;Hongni Xue;Zihan Zhang;Zekun Guo
作者机构:
College of Veterinary Medicine,Northwest A&F University,Yangling 712100,China;Key Laboratory of Animal Biotechnology,Ministry of Agriculture,Northwest A&F University,Yangling 712100,China;Xi'an Center for Disease Control and Prevention,Xi'an 710049,China
引用格式:
[1]Mengying Yu;Yingxiang Liu;Zhuo Han;Wei Du;Bingxue Chen;Lei Zhang;Hongni Xue;Zihan Zhang;Zekun Guo-.Involvement of PGC7 and UHRF1 in the regulation of DNA methylation of the IG-DMR in the imprinted Dlk1-Dio3 locus)[J].生物化学与生物物理学报(英文版),2022(07):917-930
A类:
PGC7,Dlk1,Dio3,Gtl2,chanism
B类:
Involvement,UHRF1,regulation,IG,DMR,imprinted,locus,gene,dosage,critical,growth,development,relatively,high,expression,within,especially,active,has,been,identified,only,reliable,marker,pluripotency,state,methylated,regions,which,located,upstream,dominantly,contributes,control,However,precise,mechanism,underlying,remains,largely,unknown,Here,use,F9,embryonal,carcinoma,line,low,pluripotent,model,identify,responsible,find,that,interaction,involved,maintaining,inducing,hypermethylation,cooperatively,regulate,histones,this,promotes,recruitment,DNMT1,by,between,strengthens,their,binding,H3K9me3,leads,further,enrichment,recruiting,specific,methyltransferase,SETDB1,Consequently,abundance,DNMT3A,increases,summary,propose,new,provide,insight,into,understanding,difference,levels,cells
AB值:
0.37057
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