Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex

View ORCID ProfileSimon MG Braun, Ralitsa Petrova, Jiong Tang, Andrey Krokhotin, Erik L Miller, Yitai Tang, Georgia Panagiotakos, Gerald R Crabtree
doi: https://doi.org/10.1101/2020.01.17.910794
Simon MG Braun
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA
Department of Developmental Biology, Stanford University, CA, 94305, USA
Department of Pathology, Stanford University, CA, 94305, USA
Genetic Medicine and Development Department, Faculty of Medicine, University of Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Simon MG Braun
Ralitsa Petrova
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94143, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiong Tang
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA
Department of Developmental Biology, Stanford University, CA, 94305, USA
Department of Pathology, Stanford University, CA, 94305, USA
Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*STAR), Singapore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrey Krokhotin
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA
Department of Developmental Biology, Stanford University, CA, 94305, USA
Department of Pathology, Stanford University, CA, 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erik L Miller
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA
Department of Developmental Biology, Stanford University, CA, 94305, USA
Department of Pathology, Stanford University, CA, 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yitai Tang
Department of Pathology, Stanford University, CA, 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Georgia Panagiotakos
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143, USA
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94143, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: georgia.panagiotakos@ucsf.edu crabtree@stanford.edu
Gerald R Crabtree
Howard Hughes Medical Institute, Stanford University, Stanford, CA, 94305, USA
Department of Developmental Biology, Stanford University, CA, 94305, USA
Department of Pathology, Stanford University, CA, 94305, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: georgia.panagiotakos@ucsf.edu crabtree@stanford.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Nervous system development is orchestrated by tightly-regulated progenitor cell divisions, followed by differentiation at precise but varying times across different regions. As progenitors exit the cell cycle, they initiate a subunit switch of the mSWI/SNF or npBAF complex to generate neuron-specific nBAF complexes. These chromatin regulatory complexes play dosage-sensitive roles in neural development and are frequently mutated in neurodevelopmental disorders. Here we manipulated the timing of BAF subunit exchange in the developing mouse brain and find that deletion of the npBAF subunit BAF53a blocks progenitor proliferation, leading to impaired neurogenesis. We show that npBAF complexes regulate cell cycle progression by antagonizing Polycomb complexes to promote chromatin accessibility at cell cycle and NPC identity genes. Replacement of the actin-related protein, Actl6a (BAF53a) by the neuron-specific actin-related protein, Actl6b (BAF53b), but not other regulators of proliferation, rescues progenitors by promoting neuronal differentiation. We propose that the function of the npBAF to nBAF chromatin switch is to control progenitor cell cycle exit and promote synchronous neural differentiation.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted January 17, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex
Simon MG Braun, Ralitsa Petrova, Jiong Tang, Andrey Krokhotin, Erik L Miller, Yitai Tang, Georgia Panagiotakos, Gerald R Crabtree
bioRxiv 2020.01.17.910794; doi: https://doi.org/10.1101/2020.01.17.910794
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
The npBAF to nBAF Chromatin Switch Regulates Cell Cycle Exit in the Developing Mammalian Cortex
Simon MG Braun, Ralitsa Petrova, Jiong Tang, Andrey Krokhotin, Erik L Miller, Yitai Tang, Georgia Panagiotakos, Gerald R Crabtree
bioRxiv 2020.01.17.910794; doi: https://doi.org/10.1101/2020.01.17.910794

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Developmental Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (1647)
  • Biochemistry (2741)
  • Bioengineering (1908)
  • Bioinformatics (10260)
  • Biophysics (4186)
  • Cancer Biology (3222)
  • Cell Biology (4543)
  • Clinical Trials (135)
  • Developmental Biology (2844)
  • Ecology (4472)
  • Epidemiology (2041)
  • Evolutionary Biology (7234)
  • Genetics (5478)
  • Genomics (6816)
  • Immunology (2395)
  • Microbiology (7495)
  • Molecular Biology (2996)
  • Neuroscience (18608)
  • Paleontology (136)
  • Pathology (474)
  • Pharmacology and Toxicology (781)
  • Physiology (1151)
  • Plant Biology (2710)
  • Scientific Communication and Education (682)
  • Synthetic Biology (890)
  • Systems Biology (2850)
  • Zoology (469)