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, Rosana Collepardo-Guevara, Masashi Narita, Tuomas P.J. Knowles

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article numbere202200450
JournalChemBioChem
Volume24
Issue number1
DOIs
StatePublished - Jan 3 2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Organic Chemistry

Keywords

  • HMGA
  • chromatin regulators
  • liquid-liquid phase separation
  • phase diagrams
  • protein-DNA interactions

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