Evidence map›Paper›PMID 40532700›Full record

ArticleCell2025

Bivalent chromatin instructs lineage specification during hematopoiesis.

Masaki Yagi, Gracia Bonilla, Michael S Hoetker, Nikolaos Tsopoulidis, Joy E Horng, Chuck Haggerty, Alexander Meissner, Ruslan I Sadreyev, Hanno Hock, Konrad Hochedlinger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Review
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  11. Probing the Cancer Mutational Landscape of KMT2 Regulatory Subunits.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  13. Review
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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.

Masaki YagiDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Gracia BonillaDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Michael S HoetkerDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nikolaos TsopoulidisDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joy E HorngDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chuck HaggertyMax Planck Institute for Molecular Genetics, Berlin 14195, Germany; Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
Alexander MeissnerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Max Planck Institute for Molecular Genetics, Berlin 14195, Germany; Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany.
Ruslan I SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Hanno HockCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: hock.hanno@mgh.harvard.edu.
Konrad HochedlingerDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: khochedlinger@mgh.harvard.edu.

Funding

ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6M
Roles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2011 to 2021
$20.3M
Transcription Factor Induced ReprogrammingR01HD058013 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2010 to 2019
$4.4M
Dissecting mechanistic links between MAPK signaling, genomic hypomethylation and naive pluripotencyR01HD103612 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2021 to 2025
$2.6M
Investigating the direct reprogramming of fibroblasts into skeletal muscle progenitorsR01AR077695 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2020 to 2024
$2.2M
NIAMS NIH HHS R01 AR077695NICHD NIH HHS R01 HD058013NICHD NIH HHS R01 HD103612NIDDK NIH HHS P30 DK040561NIGMS NIH HHS P01 GM099134
6 · The paper itself

Abstract

Developmental gene expression is regulated by the dynamic interplay of histone H3 lysine 4 (H3K4) and histone H3 lysine 27 (H3K27) methylation, yet the physiological roles of these epigenetic modifications remain incompletely understood. Here, we show that mice depleted for all forms of H3K4 methylation, using a dominant histone H3-lysine-4-to-methionine (H3K4M) mutation, succumb to a severe loss of all major blood cell types. H3K4M-expressing hematopoietic stem cells (HSCs) and committed progenitors are present at normal numbers, indicating that H3K4 methylation is dispensable for HSC maintenance and commitment but essential for progenitor cell maturation. Mechanistically, we reveal that H3K4 methylation opposes the deposition of repressive H3K27 methylation at differentiation-associated genes enriched for a bivalent (i.e., H3K4/H3K27-methylated) chromatin state in HSCs and progenitors. Indeed, by concomitantly suppressing H3K27 methylation in H3K4-methylation-depleted mice, we rescue the acute lethality, hematopoietic failure, and gene dysregulation. Our results provide functional evidence for the interaction between two crucial chromatin marks in mammalian tissue homeostasis.

Indexed as

ChromatinHematopoiesisHistonesAnimalsCell DifferentiationCell LineageHematopoietic Stem CellsMethylationMiceMice, Inbred C57BLChromatinHistonesbivalent genesdifferentiationH3K27MH3K27 methylationH3K4MH3K4 methylationhematopoiesishematopoietic stem and progenitor cellshistone methylationlysine-to-methionine mutation

Identifiers

PMID40532700
PMCPMC13505842

What OpenQuestion holds

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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.