Diverse DNA methylation statuses at alternative promoters of human genes in various tissues.
We characterized the DNA methylation status at 144 tissue-biased and 37 non-tissue-biased alternative promoters of 61 human genes in five normal tissues. Analysis of the collected data revealed that (i) DNA methylation status differed greatly among alternative promoters belonging to the same gene; (ii) DNA methylation status differed between tissues for the majority of the individual promoters, and (iii) 80-90% of CpG-island-containing promoters were not methylated on either allele throughout the five tissues examined. Furthermore, although the statistical significance was not as clear as for the above features, we also found that (iv) the DNA methylation patterns of tissue-biased promoters changed more drastically than those of non-tissue-biased promoters; (v) tissue-biased promoters tended to be less methylated than their respective alternative promoters in the tissues where they were preferentially expressed, and (vi) the 'null' methylation pattern of a given promoter was enriched in the tissues where the transcription was most active. These findings together indicate that there are dynamic physiological changes of DNA methylation. DNA methylation appears to play a significant role in differential usage of alternative promoters and may be related to functional diversification between CpG-island-containing promoters and CpG-island-less promoters.
Cheong
Jieun
J
Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba, Japan.
Yamada
Yoichi
Y
Yamashita
Riu
R
Irie
Takuma
T
Kanai
Akinori
A
Wakaguri
Hiroyuki
H
Nakai
Kenta
K
Ito
Takashi
T
Saito
Izumu
I
Sugano
Sumio
S
Suzuki
Yutaka
Y
D001921:Brain / Q000378:metabolism; D018899:CpG Islands / Q000502:physiology; D019175:DNA Methylation; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005796:Genes; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D012333:RNA, Messenger