Uncoupling of promoter methylation and expression of Period1 in cervical cancer cells.
We investigated possible epigenetic regulation of Period1 (PER1), a key circadian regulator gene, in six cervical cancer cell lines which showed up to 15.4-fold differences in PER1 mRNA levels. Genomic methylation analysis showed that a discerned CpG island in the PER1 promoter remained hypomethylated in five of the cell lines. In contrast, C33A cells that showed maximal PER1 expression was hypermethylated; however, demethylation treatment of C33A cells resulted in small but significant elevated PER1 mRNA levels suggesting a secondary role for promoter hypermethylation in PER1 transcriptional regulation. A discerned hypomethylated zone that harbours crucial transcriptional elements including the critical proximal E-box progressively diminished in size in the cell lines until a methylation-resistant core was retained in C33A. Our data indicate that PER1 transcription is mainly uncoupled from promoter methylation but probably involves availability and interactions of trans-acting factors with differentially methylated cis elements in the promoter hypomethylated zone.
Hsu
Min-Chuan
MC
Department of Medical Research and Education, Taipei Veterans General Hospital, Shih-Pai, Taipei, Taiwan.
Huang
Chih-Cheng
CC
Choo
Kong-Bung
KB
Huang
Chiu-Jung
CJ
D045744:Cell Line, Tumor; D019175:DNA Methylation; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D056950:Period Circadian Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D005136:Eye Proteins; C539022:PER1 protein, human; D056950:Period Circadian Proteins