Abstract
A large fraction of the animal genome is maintained in a transcriptionally repressed state throughout development. By generating viable Dnmt1(-)(/)(-) mouse cells we have been able to study the effect of DNA methylation on both gene expression and chromatin structure. Our results confirm that the underlying methylation pattern has a profound effect on histone acetylation and is the major effector of me-H3(K4) in the animal genome. We demonstrate that many methylated genes are subject to additional repression mechanisms that also impact on histone acetylation, and the data suggest that late replication timing may play an important role in this process.
Highlights
One of the main mechanisms for maintaining stable gene repression is DNA methylation
Stable Dnmt1Ϫ Fibroblasts—To evaluate how DNA methylation affects gene repression, we developed a stable somatic cell line lacking Dnmt1 activity
Effect of Undermethylation and trichostatin A (TSA) on Gene Expression— Previous microarray studies identified gene sequences that are automatically induced in Dnmt1Ϫ cells, presumably because of forced undermethylation at their promoter [17]
Summary
One of the main mechanisms for maintaining stable gene repression is DNA methylation. Using this system we surveyed a large number of individual genes in the mouse genome, analyzing their DNA methylation state, expression pattern, histone modification profile, and replication timing status.
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