PRC1 sustains the integrity of neural fate in the absence of PRC2 function
- NYU School of Medicine, United States
- New York University, United States
- NYU School of Medcine, United States
Abstract
Polycomb repressive complexes (PRCs) 1 and 2 maintain stable cellular memories of early fate decisions by establishing heritable patterns of gene repression. PRCs repress transcription through histone modifications and chromatin compaction, but their roles in neuronal subtype diversification are poorly defined. We found that PRC1 is essential for the specification of segmentally-restricted spinal motor neuron (MN) subtypes, while PRC2 activity is dispensable to maintain MN positional identities during terminal differentiation. Mutation of the core PRC1 component Ring1 in mice leads to increased chromatin accessibility and ectopic expression of a broad variety of fates determinants, including Hox transcription factors, while neuronal class-specific features are maintained. Loss of MN subtype identities in Ring1 mutants is due to the suppression of Hox-dependent specification programs by derepressed Hox13 paralogs (Hoxa13, Hoxb13, Hoxc13, Hoxd13). These results indicate that PRC1 can function in the absence of de novo PRC2-dependent histone methylation to maintain chromatin topology and postmitotic neuronal fate.
Data availability
RNAseq and ATACseq data are available through GEO (GSE175503).
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PRC1 sustains the integrity of neural fate in the absence of PRC2 functionNCBI Gene Expression Omnibus, GSE175503.
Article and author information
Author details
Esteban Orlando Mazzoni
Funding
National Institutes of Health (R35 NS116858)
- Jeremy S Dasen
National Institutes of Health (R01 NS062822)
- Jeremy S Dasen
National Institutes of Health (R01 NS097550)
- Jeremy S Dasen
National Institutes of Health (NS 100897)
- Esteban Orlando Mazzoni
National Institutes of Health (T32 GM007238)
- Ayana Sawai
National Institutes of Health (F31 NS087772)
- Ayana Sawai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paschalis Kratsios, University of Chicago, United States
Ethics
Animal experimentation: Animals work was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animal work was approved by the Institutional Animal Care and use Committee of the NYU School of Medicine in accordance to NIH guidelines.
Version history
- Received: August 4, 2021
- Preprint posted: August 10, 2021 (view preprint)
- Accepted: January 6, 2022
- Accepted Manuscript published: January 7, 2022 (version 1)
- Version of Record published: January 18, 2022 (version 2)
Copyright
© 2022, Sawai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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PRC1 sustains the integrity of neural fate in the absence of PRC2 function
eLife 11:e72769.
https://doi.org/10.7554/eLife.72769
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