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Kdm6b-mediated epigenetic coordination of temporal precision during motor neuron differentiation.

Overview

Authors: Haihan Ren1, Qicheng Liu1, Bingqian Li1, Xuetong Yu1, Dan Liang2, Shuangling Li3, Bing Pan1, Qian Gao1, Wenhong Deng4, Jun-Ma Yu5, Wenxian Wang1
  1. School of Life Sciences, Anhui Medical University, Hefei, 230032 Anhui China
  2. Department of Obstetrics and Gynecology, NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022 Anhui China
  3. Medical College, Hefei Vocational and Technical College, Hefei, 238000 Anhui China
  4. Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601 Anhui China
  5. Department of Anesthesiology, The Third Affiliated Hospital of Anhui Medical University (The First People’s Hospital of Hefei), Hefei, Anhui 230061 China
Journal: EMBO reports, volume 27, issue 13, pages 3665-3688
Dates: received 23 September 2025; accepted 15 May 2026; published online 26 May 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s44319-026-00808-2 · PMID 42192028 · PMCID PMC13354772 · OpenAlex W7162462529
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism)
Methods: Statistics
Keywords: Chromatin, Transcription & Genomics, Neuroscience
MeSH: Cell Differentiation*, Epigenesis, Genetic*, Jumonji Domain-Containing Histone Demethylases*, Motor Neurons*, Animals, Chromatin, Gene Expression Regulation, Developmental, Histones, Mice, Transcription Factors (* major topic)
Topic: Genomics and Chromatin Dynamics (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: the National Natural Science Foundation of China (32270883); The Key Program of Natural Scientific Research in Higher Education Institutions of Anhui Province (2023AH052537, 2024AH050677); The Basic and Clinical Cooperative Research Program of Anhui Medical University-Incubation Project for the Third Affiliated Hospital (2023sfy002)
Citations: not cited yet (Europe PMC); 71 references in the paper

Abstract

Histone modifiers are crucial for instructing multiple-stage cellular differentiation, yet the mechanisms underlying their temporal precision remain enigmatic. Here, we demonstrate that the H3K27 demethylase Kdm6b acts as an epigenetic regulator, coordinating stepwise motor neuron (MN) differentiation through sequential partnerships with stage-specific transcription factors (TFs). Genome-wide profiling reveals a progressive gain in Kdm6b occupancy, especially at distal regulatory elements, as differentiation proceeds. Kdm6b dynamically remodels chromatin landscapes by coordinating H3K27me3 removal with H3K27ac and H3K4me1 acquisition, thereby enabling timed gene activation from MN specification to maturation. Stage-specific inhibition of Kdm6b compromises the ordered expression of developmental genes. Mechanistically, Kdm6b interacts with temporal TFs over time to ensure precise transcriptional control and MN differentiation. Our work elucidates how a single epigenetic regulator achieves temporal fidelity of stepwise MN development, providing insight into epigenetic regulation of developmental timing.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

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Other data links

Data availability

All sequencing data generated have been deposited in Gene Expression Omnibus (GEO) database under accession number GSE306766 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306766) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306766).

The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_1038-S44319-026-00808-2 (https://www.ebi.ac.uk/biostudies/sourcedata/studies/S-SCDT-10_1038-S44319-026-00808-2).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 3 keywords, 10 MeSH terms, 3 funders, 70 references.

Cite

This paper

Ren, H., Liu, Q., Li, B., Yu, X., Liang, D., Li, S., Pan, B., Gao, Q., Deng, W., Yu, J.-M., & Wang, W. (2026). Kdm6b-mediated epigenetic coordination of temporal precision during motor neuron differentiation. EMBO reports, 27(13), 3665-3688. https://doi.org/10.1038/s44319-026-00808-2

BibTeX

@article{ren2026kdm6b,
author = {Ren, Haihan and Liu, Qicheng and Li, Bingqian and Yu, Xuetong and Liang, Dan and Li, Shuangling and Pan, Bing and Gao, Qian and Deng, Wenhong and Yu, Jun-Ma and Wang, Wenxian},
title = {{Kdm6b-mediated epigenetic coordination of temporal precision during motor neuron differentiation}},
journal = {EMBO reports},
year = {2026},
month = may,
volume = {27},
number = {13},
pages = {3665--3688},
publisher = {Nature Publishing Group},
issn = {1469-221X},
doi = {10.1038/s44319-026-00808-2},
url = {https://doi.org/10.1038/s44319-026-00808-2},
pmid = {42192028},
pmcid = {PMC13354772}
}

RIS

TY - JOUR
AU - Ren, Haihan
AU - Liu, Qicheng
AU - Li, Bingqian
AU - Yu, Xuetong
AU - Liang, Dan
AU - Li, Shuangling
AU - Pan, Bing
AU - Gao, Qian
AU - Deng, Wenhong
AU - Yu, Jun-Ma
AU - Wang, Wenxian
TI - Kdm6b-mediated epigenetic coordination of temporal precision during motor neuron differentiation
T2 - EMBO reports
J2 - EMBO Rep
PY - 2026
DA - 2026/05/26
VL - 27
IS - 13
SP - 3665
EP - 3688
SN - 1469-221X
PB - Nature Publishing Group
DO - 10.1038/s44319-026-00808-2
UR - https://doi.org/10.1038/s44319-026-00808-2
LA - en
ER -

CSL-JSON

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