Cohesin and NuRD antagonistically drive alternative neuronal fates via PLZF transcription factors.

Overview

Authors: Dongyeop Lee¹, Takashi Hirose¹, H Robert Horvitz¹

ORCID iDs: Dongyeop Lee, H Robert Horvitz

Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Institutions: Howard Hughes Medical Institute (United States); Massachusetts Institute of Technology (United States)

Journal: Science advances, volume 12, issue 31, article eaec9329

Dates: received 8 October 2025; accepted 23 June 2026; published online 31 July 2026; in print July 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1126/sciadv.aec9329 · PMID 42536746 · PMCID PMC13426411 · OpenAlex W7171972931

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: C. elegans (organism), cellular / molecular (subfield)

Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials

MeSH: Caenorhabditis elegans Proteins*, Cell Cycle Proteins*, Chromosomal Proteins, Non-Histone*, Mi-2 Nucleosome Remodeling and Deacetylase Complex*, Neurons*, Promyelocytic Leukemia Zinc Finger Protein*, Transcription Factors*, Animals, Caenorhabditis elegans, Cell Differentiation, Cohesins, Epigenesis, Genetic, GABAergic Neurons, Gene Expression Regulation, Developmental (* major topic)

Topic: Genetics, Aging, and Longevity in Model Organisms (Aging, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: NIGMS NIH HHS (R01 GM024663); NIH HHS (P40 OD010440); NCI NIH HHS (P30 CA014051)

Citations: not cited yet (Europe PMC); 95 references in the paper

Abstract

Diverse genetic and epigenetic factors cooperate to specify cellular fates during development. Establishing these fates is especially critical in the nervous system, which comprises diverse neuronal cell types. How genomic architecture interfaces with epigenetic regulators to drive transcriptional programs underlying neuronal fates remains poorly understood. Here, we show that cohesin, a protein complex that shapes genomic architecture, promotes GABAergic fate specification in a subset of neurons in the nematode Caenorhabditis elegans. This process is facilitated by EOR-1, a homolog of the human promyelocytic leukemia zinc finger (PLZF) transcription factor. The nucleosome remodeling and deacetylase (NuRD) complex and TRA-4, another PLZF homolog, promote tyraminergic fate in the normally GABAergic neurons when cohesin or EOR-1 function is lost, revealing an antagonistic mechanism determining alternative neuronal fates. These findings highlight a critical interplay among genome architecture, epigenetic remodeling, and transcriptional regulation in neuronal fate specification and, given the evolutionary conservation of these factors, suggest a mechanism underlying neural development across species.

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

Code

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The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

geo:GSE283114, at NCBI GEO; found in “Data, code, and materials availability:”

Data, code, and materials availability

The raw RNA-Seq data are available in Gene Expression Omnibus (GEO): GSE283114 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283114). All data are available in the main text or the supplementary materials. This study did not generate new code or new materials.

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

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 14 MeSH terms, 3 funders, 94 references.

Cite

This paper

Lee, D., Hirose, T., & Horvitz, H. R. (2026). Cohesin and NuRD antagonistically drive alternative neuronal fates via PLZF transcription factors. Science advances, 12(31), eaec9329. https://doi.org/10.1126/sciadv.aec9329

BibTeX

@article{lee2026cohesin, author = {Lee, Dongyeop and Hirose, Takashi and Horvitz, H Robert}, title = {{Cohesin and NuRD antagonistically drive alternative neuronal fates via PLZF transcription factors}}, journal = {Science advances}, year = {2026}, month = jul, volume = {12}, number = {31}, pages = {eaec9329}, publisher = {American Association for the Advancement of Science}, issn = {2375-2548}, doi = {10.1126/sciadv.aec9329}, url = {https://doi.org/10.1126/sciadv.aec9329}, pmid = {42536746}, pmcid = {PMC13426411} }

RIS

TY - JOUR AU - Lee, Dongyeop AU - Hirose, Takashi AU - Horvitz, H Robert TI - Cohesin and NuRD antagonistically drive alternative neuronal fates via PLZF transcription factors T2 - Science advances J2 - Sci Adv PY - 2026 DA - 2026/07/31 VL - 12 IS - 31 SP - eaec9329 SN - 2375-2548 PB - American Association for the Advancement of Science DO - 10.1126/sciadv.aec9329 UR - https://doi.org/10.1126/sciadv.aec9329 LA - en ER -

CSL-JSON

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