Global delay in nascent strand DNA methylation.

Nat Struct Mol Biol
Authors
Keywords
Abstract

Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission. Populations of arrested cells show a global reduction of lag-induced intermediate CpG methylation when compared to proliferating cells, whereas sites of transcription factor engagement appear cell-cycle invariant. Alternatively, the cancer cell line HCT116 preserves global epigenetic heterogeneity independently of cell-cycle arrest. Taken together, our data suggest that heterogeneous methylation largely reflects asynchronous proliferation, but is intrinsic to actively engaged cis-regulatory elements and cancer.

Year of Publication
2018
Journal
Nat Struct Mol Biol
Volume
25
Issue
4
Pages
327-332
Date Published
2018 04
ISSN
1545-9985
DOI
10.1038/s41594-018-0046-4
PubMed ID
29531288
PubMed Central ID
PMC5889353
Links
Grant list
P01 GM099117 / GM / NIGMS NIH HHS / United States
P50 HG006193 / HG / NHGRI NIH HHS / United States
R01 DA036898 / DA / NIDA NIH HHS / United States
RM1 HG006193 / HG / NHGRI NIH HHS / United States