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

The chromatin regulator HMGA1a undergoes phase separation in the nucleus

View ORCID ProfileHongjia Zhu, View ORCID ProfileMasako Narita, Jerelle A. Joseph, View ORCID ProfileGeorg Krainer, View ORCID ProfileWilliam E. Arter, View ORCID ProfileIoana Olan, Kadi L. Saar, Niklas Ermann, Jorge R. Espinosa, Yi Shen, Masami Ando Kuri, View ORCID ProfileRunzhang Qi, View ORCID ProfileTimothy J. Welsh, Yufan Xu, View ORCID ProfileRosana Collepardo-Guevara, View ORCID ProfileMasashi Narita, View ORCID ProfileTuomas P. J. Knowles
doi: https://doi.org/10.1101/2021.10.14.464384
Hongjia Zhu
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hongjia Zhu
Masako Narita
2Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Masako Narita
Jerelle A. Joseph
3Department of Genetics, University of Cambridge, Cambridge, UK
4Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, UK
5Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Georg Krainer
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Georg Krainer
William E. Arter
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
6Transition Bio Ltd., Maxwell Centre, JJ Thomson Avenue, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for William E. Arter
Ioana Olan
2Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ioana Olan
Kadi L. Saar
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
6Transition Bio Ltd., Maxwell Centre, JJ Thomson Avenue, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Niklas Ermann
6Transition Bio Ltd., Maxwell Centre, JJ Thomson Avenue, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jorge R. Espinosa
4Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yi Shen
7School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masami Ando Kuri
2Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Runzhang Qi
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Runzhang Qi
Timothy J. Welsh
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy J. Welsh
Yufan Xu
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rosana Collepardo-Guevara
3Department of Genetics, University of Cambridge, Cambridge, UK
4Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, UK
5Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rosana Collepardo-Guevara
  • For correspondence: rc597@cam.ac.uk masashi.narita@cruk.cam.ac.uk tpjk2@cam.ac.uk
Masashi Narita
2Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Masashi Narita
  • For correspondence: rc597@cam.ac.uk masashi.narita@cruk.cam.ac.uk tpjk2@cam.ac.uk
Tuomas P. J. Knowles
1Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
4Cavendish Laboratory, Department of Physics, University of Cambridge, J J Thomson Avenue, Cambridge, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tuomas P. J. Knowles
  • For correspondence: rc597@cam.ac.uk masashi.narita@cruk.cam.ac.uk tpjk2@cam.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The protein high mobility group A1 (HMGA1) is an important regulator of chromatin organization and function. However, the mechanisms by which it exerts its biological function are not fully understood. Here, we report that the HMGA isoform, HMGA1a, nucleates into foci that display liquid-like properties in the nucleus, and that the protein readily undergoes phase separation to form liquid condensates in vitro. By bringing together machine-leaning modelling, cellular and biophysical experiments and multiscale simulations, we demonstrate that phase separation of HMGA1a is critically promoted by protein–DNA interactions, and has the potential to be modulated by post-transcriptional effects such as phosphorylation. We further show that the intrinsically disordered C-terminal tail of HMGA1a significantly contributes to its phase separation through cation–π and electrostatic interactions. Our work sheds light on HMGA1 phase separation as an emergent biophysical factor in regulating chromatin structure.

Competing Interest Statement

G.K., W.A., N.E., and K.L.S. are employees, R.Q. is a consultant, and T.P.J.K. is a member of the board of directors at Transition Bio.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted March 04, 2022.
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 chromatin regulator HMGA1a undergoes phase separation in the nucleus
(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 chromatin regulator HMGA1a undergoes phase separation in the nucleus
Hongjia Zhu, Masako Narita, Jerelle A. Joseph, Georg Krainer, William E. Arter, Ioana Olan, Kadi L. Saar, Niklas Ermann, Jorge R. Espinosa, Yi Shen, Masami Ando Kuri, Runzhang Qi, Timothy J. Welsh, Yufan Xu, Rosana Collepardo-Guevara, Masashi Narita, Tuomas P. J. Knowles
bioRxiv 2021.10.14.464384; doi: https://doi.org/10.1101/2021.10.14.464384
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
The chromatin regulator HMGA1a undergoes phase separation in the nucleus
Hongjia Zhu, Masako Narita, Jerelle A. Joseph, Georg Krainer, William E. Arter, Ioana Olan, Kadi L. Saar, Niklas Ermann, Jorge R. Espinosa, Yi Shen, Masami Ando Kuri, Runzhang Qi, Timothy J. Welsh, Yufan Xu, Rosana Collepardo-Guevara, Masashi Narita, Tuomas P. J. Knowles
bioRxiv 2021.10.14.464384; doi: https://doi.org/10.1101/2021.10.14.464384

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

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4381)
  • Biochemistry (9581)
  • Bioengineering (7087)
  • Bioinformatics (24847)
  • Biophysics (12598)
  • Cancer Biology (9952)
  • Cell Biology (14348)
  • Clinical Trials (138)
  • Developmental Biology (7945)
  • Ecology (12103)
  • Epidemiology (2067)
  • Evolutionary Biology (15985)
  • Genetics (10921)
  • Genomics (14736)
  • Immunology (9869)
  • Microbiology (23648)
  • Molecular Biology (9477)
  • Neuroscience (50841)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2681)
  • Physiology (4013)
  • Plant Biology (8655)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2391)
  • Systems Biology (6427)
  • Zoology (1346)