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

The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes

Görkem Garipler, Congyi Lu, Alexis Morrissey, Lorena S. Lopez-Zepeda, Simon E. Vidal, Begüm Aydin, Matthias Stadtfeld, Uwe Ohler, View ORCID ProfileShaun Mahony, Neville E. Sanjana, View ORCID ProfileEsteban O. Mazzoni
doi: https://doi.org/10.1101/2020.11.23.391771
Görkem Garipler
1Department of Biology, New York University, New York, NY 10003, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Congyi Lu
1Department of Biology, New York University, New York, NY 10003, USA
2New York Genome Center, New York, NY, 10013 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexis Morrissey
3Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Penn State University, PA 16801, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lorena S. Lopez-Zepeda
4Department of Biology, Humboldt Universität zu Berlin, Berlin 10117, Germany
5Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon E. Vidal
6Skirball Institute of Biomolecular Medicine, Department of Cell Biology, NYU Langone Medical Center, New York, NY 10016, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Begüm Aydin
1Department of Biology, New York University, New York, NY 10003, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Stadtfeld
6Skirball Institute of Biomolecular Medicine, Department of Cell Biology, NYU Langone Medical Center, New York, NY 10016, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Uwe Ohler
4Department of Biology, Humboldt Universität zu Berlin, Berlin 10117, Germany
5Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin 13125, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaun Mahony
3Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Penn State University, PA 16801, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Shaun Mahony
Neville E. Sanjana
1Department of Biology, New York University, New York, NY 10003, USA
2New York Genome Center, New York, NY, 10013 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: neville@sanjanalab.org eom204@nyu.edu
Esteban O. Mazzoni
1Department of Biology, New York University, New York, NY 10003, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Esteban O. Mazzoni
  • For correspondence: neville@sanjanalab.org eom204@nyu.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

In pluripotent cells, a delicate activation-repression balance maintains pro-differentiation genes ready for rapid activation. The identity of transcription factors (TFs) that specifically repress pro-differentiation genes remains obscure. By targeting ~1,700 TFs with CRISPR loss-of-function screen, we found that ZBTB11 and ZFP131 are required for embryonic stem cell (ESC) pluripotency. ZBTB11 and ZFP131 maintain promoter-proximally paused Polymerase II at pro-differentiation genes in ESCs. ZBTB11 or ZFP131 loss leads to NELF pausing factor release, an increase in H3K4me3, and transcriptional upregulation of genes associated with all three germ layers. Together, our results suggest that ZBTB11 and ZFP131 maintain pluripotency by preventing premature expression of pro-differentiation genes and present a generalizable framework to maintain cellular potency.

One-sentence summary A Transcription Factor-wide CRISPR screen identifies ZBTB11 and ZFP131 maintaining pluripotency by pausing POL II at pro-differentiation genes

Competing Interest Statement

N.E.S. is an adviser to Vertex. S.E.V is a current employee of Genentech.

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 November 23, 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 BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes
Görkem Garipler, Congyi Lu, Alexis Morrissey, Lorena S. Lopez-Zepeda, Simon E. Vidal, Begüm Aydin, Matthias Stadtfeld, Uwe Ohler, Shaun Mahony, Neville E. Sanjana, Esteban O. Mazzoni
bioRxiv 2020.11.23.391771; doi: https://doi.org/10.1101/2020.11.23.391771
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by pausing POL II at pro-differentiation genes
Görkem Garipler, Congyi Lu, Alexis Morrissey, Lorena S. Lopez-Zepeda, Simon E. Vidal, Begüm Aydin, Matthias Stadtfeld, Uwe Ohler, Shaun Mahony, Neville E. Sanjana, Esteban O. Mazzoni
bioRxiv 2020.11.23.391771; doi: https://doi.org/10.1101/2020.11.23.391771

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 (2543)
  • Biochemistry (4994)
  • Bioengineering (3497)
  • Bioinformatics (15279)
  • Biophysics (6926)
  • Cancer Biology (5427)
  • Cell Biology (7771)
  • Clinical Trials (138)
  • Developmental Biology (4558)
  • Ecology (7180)
  • Epidemiology (2059)
  • Evolutionary Biology (10261)
  • Genetics (7532)
  • Genomics (9826)
  • Immunology (4899)
  • Microbiology (13304)
  • Molecular Biology (5165)
  • Neuroscience (29569)
  • Paleontology (203)
  • Pathology (842)
  • Pharmacology and Toxicology (1470)
  • Physiology (2153)
  • Plant Biology (4780)
  • Scientific Communication and Education (1015)
  • Synthetic Biology (1343)
  • Systems Biology (4022)
  • Zoology (771)