Evidence map›Paper›PMID 41742418›Full record

ArticleMolecular cell2026

Nucleosome spacing regulates linker methylation by DNMT3A2/3B3.

Xiaoyan Xie, Minmin Liu, Gabriella N L Chua, X Edward Zhou, Michelle L Dykstra, Shixin Liu, Peter A Jones, Evan J Worden

Abstract read
In one paragraph

Article in Molecular cell, 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

8 authors.

Xiaoyan XieVan Andel Institute, Department of Structural Biology, Grand Rapids, MI, USA.
Minmin LiuVan Andel Institute, Department of Epigenetics, Grand Rapids, MI, USA.
Gabriella N L ChuaThe Rockefeller University, Laboratory of Nanoscale Biophysics and Biochemistry, New York, NY, USA; The Rockefeller University, Laboratory of DNA Replication, Howard Hughes Medical Institute, New York, NY, USA.
X Edward ZhouVan Andel Institute, Department of Structural Biology, Grand Rapids, MI, USA.
Michelle L DykstraVan Andel Institute, Department of Structural Biology, Grand Rapids, MI, USA.
Shixin LiuThe Rockefeller University, Laboratory of Nanoscale Biophysics and Biochemistry, New York, NY, USA.
Peter A JonesVan Andel Institute, Department of Epigenetics, Grand Rapids, MI, USA.
Evan J WordenVan Andel Institute, Department of Structural Biology, Grand Rapids, MI, USA. Electronic address: evan.worden@vai.org.

Funding

Targeting DNA Methylation and the Cancer EpigenomeR35CA209859 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI PETER A JONES · 2017 to 2026
$11.9M
Epigenetic Mechanisms of Retrotransposon SilencingR35GM147261 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI Evan J Worden · 2022 to 2026
$2.4M
Biophysical Determinants of the Nucleosome as an Activity Center for Chromatin RegulatorsR01GM149862 · NIGMS · ROCKEFELLER UNIVERSITY · PI Shixin Liu · 2023 to 2026
$1.4M
Research Specialist Support-Targeting DNA Methylation and the Cancer EpigenomeR50CA243878 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI Minmin Liu · 2019 to 2026
$934k
NCI NIH HHS R35 CA209859NCI NIH HHS R50 CA243878NIGMS NIH HHS R01 GM149862NIGMS NIH HHS R35 GM147261
6 · The paper itself

Abstract

De novo CpG methylation (mCpG) is deposited by DNMT3A and DNMT3B, which target DNA linkers between nucleosomes. Cells contain millions of unique linkers, but the rules dictating which linkers get targeted by DNMT3 enzymes are not understood. We show that nucleosome spacing controls linker DNA methylation and H3K36me2 recognition by human DNMT3A2/3B3, linking de novo methylation to chromatin architecture. We present structures of DNMT3A2/3B3 bound to dinucleosomes, revealing that short linkers promote dinucleosome bridging, blocking access to linker DNA and suppressing methylation, whereas long linkers allow DNMT3A2/3B3 to engage each nucleosome separately and methylate linker DNA. Finally, we show that DNMT3A2/3B3 positions proline-tryptophan-tryptophan-proline (PWWP) domains to scan for H3K36me2. However, H3K36me2 recognition is blocked when DNMT3A2/3B3 bridges dinucleosomes with short linkers, imposing an additional structural constraint on DNMT3A2/3B3 function. Together, these findings uncover the mechanisms that govern de novo methylation in chromatin and explain how DNMT3 enzymes target linkers in cells.

Indexed as

DNADNA (Cytosine-5-)-MethyltransferasesDNA MethylationNucleosomesBinding SitesChromatinCpG IslandsDNA Methyltransferase 3ADNA Methyltransferase 3BHistonesHumansModels, MolecularProtein BindingChromatinDNADNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDNMT3A protein, humanHistonesNucleosomescancerchromatinDNA methylationDNA methyltransferasenucleosome

Identifiers

PMID41742418
PMCPMC12970607

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Registered trials

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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.