Histone tail mutants: versatile tools for decoding chromatin, development, and disease.

Masaki Yagi, Xiangle Ren, Konrad Hochedlinger

Abstract readReview

In one paragraph

Review in Trends in genetics : TIG, 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

3 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.

Xiangle RenDepartment 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.

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

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

Interrogating the role of H3K4 & H3K27 methylation in hematopoiesis with novel histone toolsR01DK145735 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Konrad Hochedlinger, Hanno R Hock · 2026 to 2026

$762k

NIAMS NIH HHS R01 AR077695NICHD NIH HHS R01 HD103612NIDDK NIH HHS R01 DK145735

6 · The paper itself

Abstract

Histone modifications have been associated with transcriptional regulation, development, and disease, yet their direct functional roles remain incompletely understood due to the redundancy and promiscuity of cognate histone-modifying enzymes. Experimental strategies based on cis- or trans-acting histone mutants, including lysine-to-methionine (K-to-M) substitutions of histone H3 and other cancer-associated oncohistone variants, enable direct interrogation of individual chromatin marks and circumvent potentially confounding effects of histone-modifying enzyme knockouts. Here, we review how histone mutants have been leveraged to uncover novel principles by which chromatin pathways govern physiological, pathological, and experimental cell fate transitions and discuss the ways in which these discoveries could be exploited in the future for therapeutic benefit.

Indexed as

cancercell identityhistone methylationhistone tail mutantsoncohistonestissue homeostasis

Identifiers

PMID42660758

DOI10.1016/j.tig.2026.08.001

PMCPMC13523005

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.