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Cited by 23Genomics and Chromatin DynamicsProtein Structure and DynamicsRNA Research and Splicing

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The Chromatin Regulator HMGA1a Undergoes Phase Separation in the Nucleus**

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Zhu, Hongjia, Narita, Masako, Joseph, Jerelle A., Krainer, Georg, Arter, William E., Olan, Ioana, Saar, Kadi L., Ermann, Niklas, Espinosa, Jorge R., Shen, Yi, Kuri, Masami Ando, Qi, Runzhang, Welsh, Timothy J., Collepardo‐Guevara, Rosana, Narita, Masashi, Knowles, Tuomas P. J.·2023·ChemBioChem
DOI 10.1002/cbic.202200450PMC PMC10098602

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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 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 electrostatic interactions via AT hooks 2 and 3. Our work sheds light on HMGA1 phase separation as an emergent biophysical factor in regulating chromatin structure.

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Metadata

Authors
Zhu, H., Narita, M., Joseph, J. A., Krainer, G., Arter, W. E., Olan, I., Saar, K. L., Ermann, N., Espinosa, J. R., Shen, Y., Kuri, M. A., Qi, R., Welsh, T. J., Collepardo‐Guevara, R., Narita, M., & Knowles, T. P. J.
Affiliations
  • University of Cambridge (GB)
  • Transition Bio Ltd., Maxwell Centre JJ Thomson Avenue Cambridge UK
  • The University of Sydney (AU)
  • Cancer Research UK Cambridge Institute Li Ka Shing Centre University of Cambridge Cambridge UK
Corresponding author
  • Collepardo‐Guevara, Rosana
  • Narita, Masashi
  • Knowles, Tuomas P. J.
ORCID
Venue
ChemBioChem
Publisher
Wiley
Published
2022-11-30
Volume
24
Issue
1
Pages
e202200450-e202200450
ISSN
  • 1439-4227 (ISSN-L)
  • 1439-7633
DOI
10.1002/cbic.202200450
PMC
PMC10098602
OpenAlex
W4308372964
Cited by
23
References
5
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 5
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
Locations
  • ChemBioChem (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
Funders
  • Cancer Research UK (C63389/A30462, A:29580, C9545, 24453, C9545/A29580, DRCQQR-NOV22/100001, 30462)
  • University of Cambridge (EP/P020259/1)
  • King's College London (EP/P020259/1)
  • European Commission (HORIZON2020)
  • China Scholarship Council (EP/P020259/1)
  • Engineering and Physical Sciences Research Council (EP/P020259/1, EP/P020259, EPSRC Tier-2 capital grant EP/P020259/1)
  • Cancer Research UK Cambridge Institute, University of Cambridge (A29580, C9545/A29580)
  • H2020 European Research Council (803326)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
HMGA1a, phase separation, chromatin organization, protein-DNA interactions, AT-hook, intrinsically disordered regions, phosphorylation, nuclear foci
MeSH terms
Cell Nucleus, Chromatin, DNA, Phosphorylation, HMGA1a Protein

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