title: Diurnal expression of Dnmt3b mRNA in mouse liver is regulated by feeding and hepatic clockwork.
abstract: 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.
authors: Center for Environmental Health Sciences, National Institute for Environmental Studies, Tsukuba, Japan.
authors: Fumihiko
authors: F
authors: Maekawa
authors: Shigeki
authors: S
authors: Shimba
authors: Shota
authors: S
authors: Takumi
authors: Tomoharu
authors: T
authors: Sano
authors: Takehiro
authors: T
authors: Suzuki
authors: Jinhua
authors: J
authors: Bao
authors: Mika
authors: M
authors: Ohwada
authors: Tatsuya
authors: T
authors: Ehara
authors: Yoshihiro
authors: Y
authors: Ogawa
authors: Keiko
authors: K
authors: Nohara
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004435:Eating / Q000235:genetics; D044127:Epigenesis, Genetic; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017440:Photoperiod; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D000097584:DNA Methyltransferase 3B
chemical_list: D056930:ARNTL Transcription Factors; D004248:DNA (Cytosine-5-)-Methyltransferases; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C538961:Bmal1 protein, mouse