The Chromatin Regulator HMGA1a Undergoes Phase Separation in the Nucleus.
Chembiochem
; 24(1): e202200450, 2023 01 03.
Article
in En
| MEDLINE
| ID: mdl-36336658
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 inâ
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatin
/
HMGA1a Protein
Type of study:
Prognostic_studies
Language:
En
Journal:
Chembiochem
Journal subject:
BIOQUIMICA
Year:
2023
Document type:
Article
Affiliation country:
Reino Unido