Evidence map›Paper›PMID 39908143›Full record

ArticleCell reports2025

KMT2C/KMT2D-dependent H3K4me1 mediates changes in DNA replication timing and origin activity during a cell fate transition.

Deniz Gökbuget, Liana Goehring, Ryan M Boileau, Kayla Lenshoek, Tony T Huang, Robert Blelloch

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
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

6 authors.

Deniz GökbugetThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: deniz.goekbuget@ucsf.edu.
Liana GoehringDepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Ryan M BoileauThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Kayla LenshoekThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Tony T HuangDepartment of Biochemistry & Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Robert BlellochThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Urology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: robert.blelloch@ucsf.edu.

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Cellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1M
Understanding the mechanistic role of genome stability pathways in regulating cell homeostasisR35GM139610 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Tony Tung Huang · 2021 to 2026
$2.6M
Rewiring of the pluripotency enhancer network during early mammalian developmentR01GM122439 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLELLOCH, ROBERT · 2017 to 2020
$1.7M
Iteratively redefining developmental potential through poised enhancersR01GM125089 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BLELLOCH, ROBERT · 2017 to 2020
$1.5M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NCI NIH HHS P30 CA016087NICHD NIH HHS T32 HD007470NIGMS NIH HHS R01 GM122439NIGMS NIH HHS R01 GM125089NIGMS NIH HHS R35 GM139610NIGMS NIH HHS T32 GM145470NIH HHS S10 OD026929
6 · The paper itself

Abstract

Mammalian genomes replicate in a cell-type-specific order during the S phase, correlated to transcriptional activity, histone modifications, and chromatin structure. The causal relationships between these features and DNA replication timing (RT), especially during cell fate changes, are largely unknown. Using machine learning, we quantify 21 chromatin features predicting local RT and RT changes during differentiation in embryonic stem cells (ESCs). About one-third of the genome shows RT changes during differentiation. Chromatin features accurately predict both steady-state RT and RT changes. Histone H3 lysine 4 monomethylation (H3K4me1), catalyzed by KMT2C and KMT2D (KMT2C/D), emerges as a top predictor. Loss of KMT2C/D or their enzymatic activities impairs RT changes during differentiation. This correlates with local H3K4me1 loss and reduced replication origin firing, while transcription remains largely unaffected. Our findings reveal KMT2C/D-dependent H3K4me1 as a key regulator of RT and replication initiation, a role that likely impacts diseases associated with KMT2C/D mutations.

Indexed as

DNA-Binding ProteinsDNA ReplicationDNA Replication TimingHistone-Lysine N-MethyltransferaseHistonesReplication OriginAnimalsCell DifferentiationCell LineageChromatinEmbryonic Stem CellsHumansLysineMethylationMiceMyeloid-Lymphoid Leukemia ProteinChromatinDNA-Binding ProteinsH3K4me1Histone-Lysine N-MethyltransferaseHistonesKmt2d protein, mouseLysineMyeloid-Lymphoid Leukemia Proteincell cyclecell fatechromatin featuresCP: Molecular biologyDNA replication domainsepiblast-like cellsepigeneticsformativegenomicsH3K4 monomethylationhistone modificationsinitiation zonesKMT2CKMT2Dmachine learningMLL3MLL4naivepluripotencypredictive modelingreplication originsreplication timingtranscription

Identifiers

PMID39908143
PMCPMC12140508

What OpenQuestion holds

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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.