---
title: "PHC2-Dependent PRC1 Assemblies Stabilize Motor Neuron Hox Codes"
id: "biorxiv-4-phc2-dependent-prc1-assemblies-stabilize-motor-neuron-hox-codes"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-phc2-dependent-prc1-assemblies-stabilize-motor-neuron-hox-codes"
content_type: "clinical_feed_article"
specialty: "Neurology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1?rss=1"
published_at: "2026-10-07T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# PHC2-Dependent PRC1 Assemblies Stabilize Motor Neuron Hox Codes
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-phc2-dependent-prc1-assemblies-stabilize-motor-neuron-hox-codes
- **Specialty:** [Neurology](https://medichelpline.com/clinical-feed/neurology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1?rss=1)
- **Published At:** 2026-10-07T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Polycomb Repressive Complex 1 (**PRC1**) and PRC2 organize chromatin to control cell-type specific gene expression; in the developing spinal cord PRC1 is essential for Hox-dependent programs that specify motor neuron identities. - Canonical PRC1 subunits—**BMI1**, **PHC2**, CBX2, and RING1B—form subnuclear assemblies as neural progenitors differentiate into motor neurons in chick and mouse models. - Experimentally disrupting **PHC2** polymerization in neural progenitors or postmitotic neurons dismantles BMI1-containing PRC1 assemblies and causes derepression of caudal **Hox** genes, producing a cell-autonomous loss of segment-specific motor neuron fates. - Mouse mutants lacking the core PRC1 subunit Ring1 cannot form BMI1-containing assemblies despite intact PHC2 and CBX2 polymers, indicating additional core subunits are required for BMI1 assembly incorporation. - Neuron-restricted deletion of core PRC2 subunits (Ezh1/2) depletes **H3K27me3** marks but preserves PRC1 assemblies and Hox expression boundaries, suggesting PRC1 assemblies can stabilize Hox codes independently of PRC2-mediated H3K27 methylation. - Overall, the data support a model in which **PHC2**-dependent PRC1 subnuclear assemblies stabilize Hox transcriptional boundaries and maintain motor neuron segmental identities during differentiation.
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Alexander K Miller NYU Grossman School of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Alexander%2BK%2BMiller%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Miller%20AK&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAlexander%2BK%2BMiller%2B) Ayana Sawai NYU Grossman School of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ayana%2BSawai%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Sawai%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAyana%2BSawai%2B) Anne E Cavanagh NYU Grossman School of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Anne%2BE%2BCavanagh%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Cavanagh%20AE&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnne%2BE%2BCavanagh%2B) Jeremy S Dasen NYU Grossman School of Medicine * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jeremy%2BS%2BDasen%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Dasen%20JS&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AJeremy%2BS%2BDasen%2B) * [ORCID record for Jeremy S Dasen](http://orcid.org/0000-0002-9434-874X "Open in new tab") * For correspondence: jeremy.dasen@nyulangone.org * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5846163/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5846163/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5846163/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5846163/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.06.757095v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5846163/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Polycomb Repressive Complexes PRC1 and PRC2 establish and maintain chromatin architectures critical for cell-type specific gene expression. In the developing spinal cord, PRC1 is essential for implementing Hox-dependent transcriptional programs that diversify motor neuron identities. Although PRC1 can assemble into subnuclear condensates, whether these structures contribute to the specification and maintenance of neuronal subtype fates remains unclear. Using chick and mouse models, we show that canonical PRC1 components - BMI1, PHC2, CBX2, RING1B - coalesce into subnuclear assemblies as neural progenitors differentiate into motor neurons. Disrupting PHC2 polymerization in either neural progenitors or postmitotic neurons dismantles BMI1-containing PRC1 assemblies, triggering derepression of caudal Hox genes and a cell autonomous loss of segment-specific motor neuron fates. Mouse mutants lacking the core PRC1 subunit Ring1 fail to form BMI1-containing assemblies, despite intact PHC2 and CBX2 polymers. In contrast, motor neuron-restricted deletion of core PRC2 subunits (Ezh1/2) depletes H3K27me3 histone marks but retains PRC1 assemblies and Hox boundaries. Together, these findings indicate that PHC2-dependent PRC1 assemblies stabilize Hox transcriptional boundaries and motor neuron segmental identities. ### Competing Interest Statement The authors have declared no competing interest. ## Funder Information Declared National Institute of Neurological Disorders and Stroke, 5R35NS116858, 5T32HD007520 National Cancer Institute, P30CA016087 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. 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