The Chromatin Regulator HMGA1a Undergoes Phase Separation in the Nucleus. (30th November 2022)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Chembiochem. Volume 24:Number 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-30
• Subjects: chromatin regulators -- HMGA -- liquid-liquid phase separation -- phase diagrams -- protein-DNA interactions; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200450
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : The liquid‐liquid phase separation (LLPS) behaviour of the high mobility group A1a (HMGA1a) is presented. As an important chromatin regulator protein, HMGA1a can interact with DNA molecules and readily forms liquid condensates. This sheds light on its new biophysical role in regulating chromatin.