Evidence map›Paper›PMID 41786706›Full record

ArticleNature communications2026

Molecular basis for the inhibition of de novo DNA methylation by TCL1A.

Qingting Liu, Jinhong Li, Xiaoxiao Wang, Yaozong Li, Yu Wu, Zhuo Han, Zixin Guo, Li Guo, Xiang Wang, Gang Yuan and 3 more

Abstract read
PubMed Full text at PMC Publisher
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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

13 authors.

Qingting Liu *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Jinhong Li *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Xiaoxiao Wang *The Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Yaozong Li *Department of Chemistry, Umeå University, Umeå, Sweden.ORCID 0000-0002-5796-2644
Yu WuThe Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhuo HanDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.ORCID 0000-0003-0466-4122
Zixin GuoDepartment of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.
Li GuoDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Xiang WangDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.ORCID 0000-0001-9348-7441
Gang YuanDepartment of Thoracic Surgery and Institute of Thoracic Oncology, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China; Western China Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer, Sichuan University, Chengdu, China.
Zheng GaoDepartment of Obstetrics and Gynecology, Center for Reproductive Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. gaozheng@gzhmu.edu.cn.ORCID 0000-0002-8264-6002
Lei LiThe Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. lil@ioz.ac.cn.ORCID 0000-0001-5478-5681
Dong DengDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China. dengd@scu.edu.cn.ORCID 0000-0002-8590-9525

Funding

National Natural Science Foundation of China (National Science Foundation of China) 2021A1515011011National Natural Science Foundation of China (National Science Foundation of China) 2023NSFSC0017National Natural Science Foundation of China (National Science Foundation of China) 82271682Vetenskapsrådet (Swedish Research Council) Grant VR 2019-00608
6 · The paper itself

Abstract

DNA methyltransferases DNMT3A/B mediate de novo DNA methylation, essential for embryonic development and cell fate determination. Dysregulation of DNMT3A/B causes developmental defects and tumorigenesis. TCL1A is critical for embryogenesis but promotes lymphomagenesis when deregulated. Previous studies suggested TCL1A binds DNMT3A/B and inhibits their activity, but the mechanism remained unclear. Here, we report the cryo-EM structure of the DNMT3A-TCL1A complex, which comprises a DNMT3A dimer bound by two TCL1A dimers. TCL1A interacts with the catalytic domain of DNMT3A, overlapping with the DNMT3L-binding site, and induces extended conformational rearrangements. The target recognition domain and catalytic loop shift markedly, reducing DNA accessibility, while the catalytic loop occupies the SAM-binding pocket, thereby blocking methyltransferase activity. Supported by biochemical assays and molecular dynamics simulations, we propose a dynamic inhibition mechanism in which TCL1A exploits DNMT3A conformational plasticity to suppress de novo DNA methylation.

Indexed as

DNA (Cytosine-5-)-MethyltransferasesDNA MethylationProto-Oncogene ProteinsAnimalsBinding SitesCatalytic DomainCryoelectron MicroscopyDNA Methyltransferase 3AHumansMolecular Dynamics SimulationProtein BindingDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanProto-Oncogene ProteinsTCL1A protein, human

Identifiers

PMID41786706
PMCPMC12963412

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.