期刊
MECHANISMS OF AGEING AND DEVELOPMENT
卷 123, 期 9, 页码 1257-1268出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0047-6374(02)00014-3
关键词
DNA methylation; ITGAL; LFA-1; T lymphocytes; aging
资金
- NIAID NIH HHS [AI42753] Funding Source: Medline
- NIAMS NIH HHS [AR42525] Funding Source: Medline
- NIA NIH HHS [AG014783] Funding Source: Medline
DNA methylation patterns change with age in a complex fashion, typically with an overall decrease in genomic deoxymethylcytosine (d(m)C) content, but with local increases in some promoters that contain GC-rich sequences known as CpG islands. While the consequences of age-dependent CpG island methylation have recently been studied in organs such as the colon, less is known about the functional significance of the progressive hypomethylation of promoters lacking CpG islands, and the significance of age-dependent changes in T cell DNA methylation is completely unexplored. We asked if age-dependent DNA hypornethylation might contribute to overexpression of the T cell ITGAL gene, which encodes CD11a, a subunit of LFA-1. CD11a mRNA increased with age as well as with experimentally induced DNA hypomethylation. This increase correlated with hypomethylation of sequences flanking the ITGAL promoter in vitro and in aging. 'Patch' methylation of the region suppressed promoter function. DNA methyltransferases 1 and 3a also decreased with aging. These results indicate that hypomethylation of regions flanking the ITGAL promoter may increase CD11a expression, and suggest that age-dependent hypomethylation of promoters lacking CpG islands, perhaps due to decreased DNA methyltransferase expression, may be one mechanism contributing to increased T cell gene expression with aging. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据