Document Detail

Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork.
MedLine Citation:
PMID:  22847467     Owner:  NLM     Status:  MEDLINE    
DNA methyltransferase 3B (DNMT3B) is critically involved in de novo DNA methylation and genomic stability, while the regulatory mechanism in liver is largely unknown. We previously reported that diurnal variation occurs in the mRNA expression of Dnmt3b in adult mouse liver. The aim of this study was to determine the mechanism underlying the diurnal expression pattern. The highest level and the lowest level of Dnmt3b mRNA expression were confirmed to occur at dawn and in the afternoon, respectively, and the expression pattern of Dnmt3b closely coincided with that of Bmal1. Since the diurnal pattern of Dnmt3b mRNA expression developed at weaning and scheduled feeding to separate the feeding cycle from the light/dark cycle led to a phase-shift in the expression, it could be assumed that feeding plays a critical role as an entrainment signal. In liver-specific Bmal1 knockout (L-Bmal1 KO) mice, L-Bmal1 deficiency resulted in significantly higher levels of Dnmt3b at all measured time points, and the time when the expression was the lowest in wild-type mice was shifted to earlier. Investigation of global DNA methylation revealed a temporal decrease of 5-methyl-cytosine percentage in the genome of wild-type mice in late afternoon. By contrast, no such decrease in 5-methyl-cytosine percentage was detected in L-Bmal1 KO mice, suggesting that altered Dnmt3b expression affects the DNA methylation state. Taken together, the results suggest that the feeding and hepatic clockwork generated by the clock genes, including Bmal1, regulate the diurnal variation in Dnmt3b mRNA expression and the consequent dynamic changes in global DNA methylation.
Fumihiko Maekawa; Shigeki Shimba; Shota Takumi; Tomoharu Sano; Takehiro Suzuki; Jinhua Bao; Mika Ohwada; Tatsuya Ehara; Yoshihiro Ogawa; Keiko Nohara
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-31
Journal Detail:
Title:  Epigenetics : official journal of the DNA Methylation Society     Volume:  7     ISSN:  1559-2308     ISO Abbreviation:  Epigenetics     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-06-14     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101265293     Medline TA:  Epigenetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1046-56     Citation Subset:  IM    
Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba, Japan.
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MeSH Terms
ARNTL Transcription Factors / genetics,  metabolism
Biological Clocks / genetics
Circadian Rhythm / genetics*
DNA (Cytosine-5-)-Methyltransferase / genetics*,  metabolism
DNA Methylation
Eating / genetics
Epigenesis, Genetic*
Liver / metabolism*
Mice, Inbred C57BL
RNA, Messenger / metabolism
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/Arntl protein, mouse; 0/RNA, Messenger; EC (Cytosine-5-)-Methyltransferase; EC methyltransferase 3B

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