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Effects of histone acetylation and DNA methylation on p21^(WAF1)regulation

查看全文 作　　者：[1]FangJY;[2]LuYY 高影响力作者 机构地区：[1]RenjiHospital,ShanghaiInstituteofDigestiveDisease,ShanghaiSecondMedicalUniversity,Shanghai,China;[2]BeijingCancerInstitute,BeijingUniversity,Beijing100000高影响力机构 出　　处：《World Journal of Gastroenterology》索引2002年第8卷第3期,共6页高影响力期刊 摘　　要：Cell cycle progression is regulated by interactions betweencyclins and cyclin-dependent kinases (CDKs). p21wAF1 is oneof the CIP/KIP family which inhibits CDKs activity. Increasedexpression of p21WAF1 may play an important role in thegrowth arrest induced in transformed calls. Although thestability of the p21wAF1 mRNA could be altered by differentsignals, cell differentiation and numerous influencingfactors. However, recent studies suggest that two knownmechanisms of epigenesis, i. e. gene inactivation bymethylation in promoter region and changes to an inactivechromatin by histone deacetylation, seem to be the bestcandidate mechanisms for inactivation of p21WAF1. To date,almost no coding region p21wAF1 mutations have been foundin tumor cells, despite extensive screening of hundreds ofvarious tumors. Hypermethylation of the p21WAF1 promoterregion may represent an alternative mechanism by which thep21WAF1/ClPl gene can be inactivated. The reduction of cellularDNMT protein levels also induces a corresponding rapidincrease in the cell cycle regulator p21wAF1 proteindemonstrating a regulatory link between DNMT and p21WAF1which is independent of methylation of DNA. Both histonehyperacetylation and hypoacetylation appear to be importantin the carcinoma process, and induction of the p21WAF1 geneby histone hyperacetylation may be a mechanism by whichdietary fiber prevents carcinogenesis. Here, we review theinfluence of histone acetylation and DNA methylation onp21WAF1 transcription, and affection of pathways or factorsassociated such as p53, E2A, Sp1 as well as several histonedeacetylation inhibitors. 关 键 词：组蛋白 乙酰化 DNA 甲基化 P21^WAF1基因
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