CpG site DNA methylation patterns reveal a novel regulatory element in the mouse prion protein gene.
The cellular isoform of the prion protein (PrPC) plays critical roles in the development of prion disorders. Although PrP mRNA is ubiquitously present in a tissue-specific manner, the DNA methylation of PrP gene (Prnp) is still unknown. In this study, we demonstrated that the CpG island (CGI, positioned at -218 to +152 bp from the transcriptional start site) including the Prnp core promoter region was completely unmethylated in all tested tissues. On the other hand, CpG methylation in the CGI shore region (positioned at -599 to -238 bp) occurred in various tissue- and site-specific proportions. Interestingly, the correlation analysis between CpG methylation status and PrP mRNA levels showed that one CpG site methylation at -576 was negatively correlated with the PrP mRNA level (Pearson's r = -0.374, P=0.035). Taken together, our results suggest that Prnp is a typical housekeeping gene and various methylation frequencies of the CGI shore region are likely to affect Prnp expression in a tissue-specific manner.
Laboratory of Microbiology and Immunology, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
Wuyun
W
Dalai
Eiko
E
Matsuo
Natsumi
N
Takeyama
Junichi
J
Kawano
Keiichi
K
Saeki
D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D000072002:Prion Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D000072002:Prion Proteins; C512657:Prnp protein, mouse; D012333:RNA, Messenger
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