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

Genomics. 2007 Mar;89(3):326-37. doi: 10.1016/j.ygeno.2006.11.006. Epub 2006 Dec 26.


Alterations in DNA methylation have been implicated in mammalian development. Hence, the identification of tissue-specific differentially methylated regions (TDMs) is indispensable for understanding its role. Using restriction landmark genomic scanning of six mouse tissues, 150 putative TDMs were identified and 14 were 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, is further analyzed in nine 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Base Sequence
  • CpG Islands / genetics
  • DEAD-box RNA Helicases / genetics
  • DNA Methylation*
  • Gene Expression Regulation*
  • Genome, Human
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Organ Specificity*
  • Spermatogenesis
  • Testis / metabolism


  • DDX4 protein, human
  • Ddx4 protein, mouse
  • DEAD-box RNA Helicases