期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 1, 页码 158-176出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa1169
关键词
-
资金
- BW Foundation [BWST-ncRNA-007]
- University of Stuttgart
This study revealed that DNA methylation introduced in CGIs can significantly decrease gene expression, and is associated with a global decrease in H3K4me3 and H3K27ac, while being stable at some CGIs. The results highlight the importance of genome-wide molecular processes that protect CGIs against DNA methylation.
Chromatin properties are regulated by complex networks of epigenome modifications. Currently, it is unclear how these modifications interact and if they control downstream effects such as gene expression. We employed promiscuous chromatin binding of a zinc finger fused catalytic domain of DNMT3A to introduce DNA methylation in HEK293 cells at many CpG islands (CGIs) and systematically investigated the dynamics of the introduced DNA methylation and the consequent changes of the epigenome network. We observed efficient methylation at thousands of CGIs, but it was unstable at about 90% of them, highlighting the power of genome-wide molecular processes that protect CGIs against DNA methylation. Partially stable methylation was observed at about 1000 CGIs, which showed enrichment in H3K27me3. Globally, the introduced DNA methylation strongly correlated with a decrease in gene expression indicating a direct effect. Similarly, global but transient reductions in H3K4me3 and H3K27ac were observed after DNA methylation but no changes were found for H3K9me3 and H3K36me3. Our data provide a global and time-resolved view on the network of epigenome modifications, their connections with DNA methylation and the responses triggered by artificial DNA methylation revealing a direct repressive effect of DNA methylation in CGIs on H3K4me3, histone acetylation, and gene expression.
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