Epigenetic regulation of the circadian clock: Role of 5-aza-2'-deoxycytidine
2017
We have been investigating transcriptional regulation of the
BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of
BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the
BMAL1 and the
PER2 promoters were hyper- and hypo-methylated, respectively and that 5-aza-29-deoxycytidine (aza-dC) not only enhanced
PER2 gene expression but also
PER2 oscillation within 24 hours in RPMI8402 cells. That is, such hypermethylation of CpG islands in the
BMAL1
promoter restricted
PER2 expression that was recovered by aza-dC within one day in these cells. These results suggest that the circadian clock system can be recovered through
BMAL1 expression induced by aza-dC within a day. The
RPIB9 promoter of RPMI8402 cells, which is a methylation hotspot in lymphoblastic leukemia, was also hypermethylated, and aza-dC gradually recovered
RPIB9 expression in three days. In addition, methylation-specific PCR revealed a different degree of aza-dC-induced methylation release by between
BMAL1 and
RPIB9
. These results suggest that the aza-dC-induced recovery of gene expression from DNA methylation is dependent on a gene, for example, the rapid response to demethylation by the circadian system, and thus is of importance to clinical strategies for treating cancer.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
49
References
11
Citations
NaN
KQI