NSD2 Coordinates the Neurogenic-to-Gliogenic Transition via H3K36me2-Dependent Activation of the EGFR-ERK Pathway.
Overview
- State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Biochemistry & Molecular Biology, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Abstract
Haploinsufficiency of the histone methyltransferase NSD2 is a major cause of Wolf‐Hirschhorn syndrome (WHS) and the related Rauch‐Steindl syndrome (RAUST), both of which exhibit microcephaly and intellectual disability. However, the precise role of NSD2 in brain development remains unclear. Here, we identify NSD2 as a pivotal epigenetic regulator orchestrating the transition from neurogenesis to gliogenesis in the developing mouse neocortex. Conditional knockout of Nsd2 severely impairs astrocyte production in late embryogenesis, while its overexpression promotes astrocytic fate. Integrated epigenomic and transcriptomic analyses reveal that NSD2 deposits the activating histone mark H3K36me2 directly at the Egfr promoter, sustaining EGFR expression and downstream ERK signaling—a pathway essential for gliogenesis. Pharmacological activation of ERK phosphorylation rescues the astrogliogenesis defects both in vitro and in vivo. Notably, Nsd2‐deficient mice exhibit significant deficits in learning and memory. Our findings define an NSD2‐H3K36me2‐EGFR‐ERK axis that drives cortical gliogenesis and provide mechanistic insights into the potential contribution of NSD2 deficiency to neurodevelopmental abnormalities.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE232566, at NCBI GEO; found in “Data Availability Statement”
Data Availability Statement
The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive (Genomics, Proteomics & Bioinformatics 2025) in National Genomics Data Center (Nucleic Acids Res 2025), China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences (GSA: CRA044655) that are publicly accessible at https://
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, 27 September 2026: the first record
Recorded: type, language, journal, pages, dates, 8 authors, 5 keywords, 7 funders, 59 references.
Cite
This paper
Chen, H., Li, M., Hou, L., Yin, B., Qiang, B., Gao, R., Shu, P., & Peng, X. (2026). NSD2 Coordinates the Neurogenic-to-Gliogenic Transition via H3K36me2-Dependent Activation of the EGFR-ERK Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e76695. https://
BibTeX
@article{chen2026nsd2,
author = {Chen, Hanxue and Li, Mengyuan and Hou, Lin and Yin, Bin and Qiang, Boqin and Gao, Ran and Shu, Pengcheng and Peng, Xiaozhong},
title = {{NSD2 Coordinates the Neurogenic-to-Gliogenic Transition via H3K36me2-Dependent Activation of the EGFR-ERK Pathway}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = jul,
pages = {e76695},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42505068},
pmcid = {PMC13403718}
}
RIS
TY - JOUR
AU - Chen, Hanxue
AU - Li, Mengyuan
AU - Hou, Lin
AU - Yin, Bin
AU - Qiang, Boqin
AU - Gao, Ran
AU - Shu, Pengcheng
AU - Peng, Xiaozhong
TI - NSD2 Coordinates the Neurogenic-to-Gliogenic Transition via H3K36me2-Dependent Activation of the EGFR-ERK Pathway
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
SP - e76695
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
{
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"family": "Shu",
"given": "Pengcheng"
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"family": "Peng",
"given": "Xiaozhong"
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"URL": "https://
"language": "en",
"issued": {
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