Year: 2022
Type: article
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.
Source: ChemBioChem
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,900
Awards: G1847806088, Peta-5: A National Facility for Petascale Data Intensive Computation and Analytics, G279312593, G3004532622, G358276009, G434337789, G4911007465, G6017516655, G63586632, G6661763476, G6691532168, G7347995879, G7669185616, G797072831, G8228709867, Towards Realistic Modelling of Nucleosome Organization Inside Functional Chromatin Domains, G8989788551
OpenAlex ID: W4308372964