Evidence map›Paper›PMID 42901900›Full record

ArticleNature communications2026

The DNMT1 CXXC domain senses CpG islands for DNA methylation inhibition.

Jian Fang, Bo Pan, Wendan Ren, Jiuwei Lu, Ting Zhao, Yiran Guo, Ling Cai, Yinsheng Wang, Gang Greg Wang, Jikui Song

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Jian Fang *Department of Biochemistry, University of California, Riverside, CA, USA.ORCID 0000-0002-8652-1768
Bo Pan *Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0002-2626-1589
Wendan Ren *Department of Biochemistry, University of California, Riverside, CA, USA.
Jiuwei LuDepartment of Biochemistry, University of California, Riverside, CA, USA.ORCID 0000-0002-6478-4081
Ting ZhaoEnvironmental Toxicology Graduate Program, University of California, Riverside, CA, USA.
Yiran GuoDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
Ling CaiDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0003-1240-3045
Yinsheng WangEnvironmental Toxicology Graduate Program, University of California, Riverside, CA, USA.
Gang Greg WangDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA. greg.wang@duke.edu.ORCID 0000-0002-7210-9940
Jikui SongDepartment of Biochemistry, University of California, Riverside, CA, USA. jikui.song@ucr.edu.ORCID 0000-0002-4958-1032

Funding

Mechanistic Insights into Mammalian DNA MethylationR35GM119721 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Jikui Song · 2016 to 2026
$5.3M
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R35GM119721
6 · The paper itself

Abstract

DNA methyltransferase DNMT1 plays an essential role in maintaining DNA methylation homeostasis. While DNMT1-mediated DNA methylation mainly occurs outside the active chromatin domains, such as CpG islands, how DNMT1 interplays with hypomethylated nucleosome environment to restrict CpG island methylation remains unclear. Here we report the structure of DNMT1 with a nucleosome containing unmodified CpG sites. The interaction of the DNMT1 CXXC domain with the unmodified CpG sites within the nucleosome core or the linker strengthens the DNMT1-nucleosome association, which contributes to the enrichment of DNMT1 in CpG islands. On the other hand, the CXXC domain is positioned in a manner that blocks the target recognition domain of DNMT1 from accessing potential DNA substrates. Consistently, disrupting the CXXC-CpG interaction leads to DNMT1 hyperactivity on nucleosomes with unmodified CpG sites, or those with spatially proximate unmodified and hemimethylated CpG sites. Furthermore, our whole-genome bisulfite-sequencing analysis reveals that introducing the CXXC-CpG interaction-defective DNMT1 mutation leads to substantial increase in CpG island methylation but not so much in overall genomic methylation, causing severe defects in transcriptional programming and stem cell differentiation. Together, this study establishes a role for the CXXC domain in safeguarding the CpG island hypomethylation, vital to DNA methylation homeostasis during development.

Indexed as

CpG IslandsDNA (Cytosine-5-)-Methyltransferase 1DNA MethylationAnimalsCell DifferentiationHumansMutationNucleosomesProtein BindingProtein DomainsDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanNucleosomes

Identifiers

PMID42901900
PMCPMC13683344

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.