1. Developmental Biology
  2. Neuroscience
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PRC1 sustains the integrity of neural fate in the absence of PRC2 function

  1. Ayana Sawai
  2. Sarah Pfennig
  3. Milica Bulajić
  4. Alexander Miller
  5. Alireza Khodadadi-Jamayran
  6. Esteban Orlando Mazzoni
  7. Jeremy S Dasen  Is a corresponding author
  1. NYU School of Medicine, United States
  2. New York University, United States
  3. NYU School of Medcine, United States
Research Article
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Cite this article as: eLife 2022;11:e72769 doi: 10.7554/eLife.72769

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).

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Ayana Sawai

    Department of Neuroscience and Physiology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5446-4930
  2. Sarah Pfennig

    Department of Neuroscience and Physiology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Milica Bulajić

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander Miller

    Department of Neuroscience and Physiology, NYU School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alireza Khodadadi-Jamayran

    Applied Bioinformatics Laboratories, NYU School of Medcine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Esteban Orlando Mazzoni

    Department of Biology, New York University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8994-681X
  7. Jeremy S Dasen

    Department of Neuroscience and Physiology, NYU School of Medicine, New York, United States
    For correspondence
    Jeremy.Dasen@nyumc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9434-874X

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.

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.

Reviewing Editor

  1. Paschalis Kratsios, University of Chicago, United States

Publication history

  1. Received: August 4, 2021
  2. Accepted: January 6, 2022
  3. Accepted Manuscript published: January 7, 2022 (version 1)

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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