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 PERI 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 PERI 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. (c) 2007 Elsevier Inc. All rights reserved.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Volume: 360 Issue: 1 Pages: 257-262
