DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter
xianglanxue 添加于 2011-10-10 09:58
| 1874 次阅读 | 0 个评论
作 者
Han H, Cortez CC, Yang X, Nichols PW, Jones PA, Liang G 摘 要
Despite the fact that 45% of all human gene promoters do not contain CpG islands, the role of DNA methylation in control of non-CpG island promoters is controversial and its relevance in normal and pathological processes is poorly understood. Among the few studies which investigate the correlation between DNA methylation and expression of genes with non-CpG island promoters, the majority do not support the view that DNA methylation directly leads to transcription silencing of these genes. Our reporter assays and gene reactivation by 5-aza-2'-deoxycytidine, a DNA demethylating agent, show that DNA methylation occurring at CpG poor LAMB3 promoter and RUNX3 promoter 1(RUNX3 P1) can directly lead to transcriptional silencing in cells competent to express these genes in vitro. Using Nucleosome Occupancy Methylome- Sequencing, NOMe-Seq, a single-molecule, high-resolution nucleosome positioning assay, we demonstrate that active, but not inactive, non-CpG island promoters display a nucleosome-depleted region (NDR) immediately upstream of the transcription start site (TSS). Furthermore, using NOMe-Seq and clonal analysis, we show that in RUNX3 expressing 623 melanoma cells, RUNX3 P1 has two distinct chromatin configurations: one is unmethylated with an NDR upstream of the TSS; another is methylated and nucleosome occupied, indicating that RUNX3 P1 is monoallelically methylated. Together, these results demonstrate that the epigenetic signatures comprising DNA methylation, histone marks and nucleosome occupancy of non-CpG island promoters are almost identical to CpG island promoters, suggesting that aberrant methylation patterns of non-CpG island promoters may also contribute to tumorigenesis and should therefore be included in analyses of cancer epigenetics.-
详细资料
- 文献种类:期刊
- 期刊名称: Human Molecular Genetics
- 期刊缩写: Hum Mol Genet
- 期卷页: 2011年
- 地址: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy
- ISBN: 0964-6906
评论( 人)
相关链接
DOI URL
Nucleosome positioning and gene regulation: advances through genomics
浙公网安备 33010202000686号 ( 浙ICP备09035230号-1 )
