Journal
GENOMICS
Volume 89, Issue 3, Pages 326-337Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2006.11.006
Keywords
DNA methylation; tissues; CpG islands; bisulfites; DDX4; gene expression; testis; spermatocytes; gene expression regulation; human genome
Funding
- NCI NIH HHS [R01 CA102423, CA16056, R01 CA102423-01A1, P30 CA016056, CA102423] Funding Source: Medline
- NIEHS NIH HHS [R01 ES012249-03] Funding Source: Medline
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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. (c) 2006 Elsevier Inc. All rights reserved.
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