title: Silencing of the CKII alpha and CKII alpha' genes during cellular senescence is mediated by DNA methylation.
abstract: Previously we reported that down-regulation of CKII activity is tightly associated with cellular senescence and that the mRNA and protein levels of CKII alpha decrease during senescence. The present study demonstrates that the mRNA and protein levels of CKII alpha' also decrease during senescence. Knockdown of CKII alpha' in IMR-90 cells by RNA interference induced the senescent phenotype. Treatment of senescent IMR-90 cells with a demethylating agent 5-aza-2'-deoxycytidine induced CKII alpha and CKII alpha' expression, suggesting that DNA hypermethylation might be involved in the silencing of CKII alpha and CKII alpha' genes in senescent cells. However, bisulfite sequencing analysis revealed that the methylation status of the CpG islands within the reported CKII alpha and CKII alpha' promoters was not associated with senescence. Instead, senescence-dependent hypermethylation was observed in the region ranging from position +1112 to +1128 of the CKII alpha gene and at positions -527 and +829 of the CKII alpha' gene. In addition, this study indicates that DNA methylation-dependent down-regulation of transcription factors Sp1, Ets1 and NF-kappaB might be involved in silencing of the CKII alpha and CKII alpha' genes during cellular senescence.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kyungpook National University Daegu 702-701, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kang
authors.forename: Yoon-Hwa
authors.initials: YH
authors.lastname: Rho
authors.forename: Yun Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Dong-Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D001374:Azacitidine / Q000494:pharmacology; D047390:Casein Kinase II / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D047390:Casein Kinase II; D001374:Azacitidine