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Elsevier, Genomics, 3(89), p. 326-337, 2007

DOI: 10.1016/j.ygeno.2006.11.006

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Analysis of tissue-specific differentially methylated regions (TDMs) in humans

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Alterations in DNA methylation have been implicated in mammalian development. Hence the identification of the tissue-specific differentially methylated regions (TDMs) is indispensable for understanding its role. Using restriction landmark genomic scanning (RLGS) of 6 mouse tissues, 150 putative TDMs were identified and 14 further analyzed. The DNA sequences of the 14 mouse TDMs are analyzed in this study. Six of the human homologous regions show TDMs to both mouse and human, and genes in five of these regions have conserved tissue-specific expression; preferential expression in testis. A TDM, DDX4, are further analyzed in 9 testis tissues. An increase in methylation of the promoter region is significantly associated with a marked reduction of the gene expression and defects in spermatogenesis, suggesting that hypomethylation of the DDX4 promoter region regulates DDX4 gene expression in spermatogenic cells. Our results indicate that some genomic regions with tissue-specific methylation and expression are conserved between mouse and human, and suggest that DNA methylation may have an important role in regulating differentiation and tissue/cell-specific gene expression of some genes.