Biology subjects

Marr, S. K.

Publications and source records attributed to Marr, S. K..

3 recordsLinked to original sources

bioRxiv2025

Mutual Antagonism Between PRC1 Condensates and SWI/SNF in Chromatin Regulation

Opposing activities of conserved chromatin regulatory complexes, such as the Polycomb Repressive Complex 1 (PRC1) and the activating chromatin remodeler SWI/SNF play critical roles in regulating gene expression during development and differentiation. The mechanisms by which these complexes compete to regulate chromatin states remain poorly understood. We combine single-molecule analysis and genomic approaches in cultured cells to demonstrate that the condensate-forming properties of PRC1 play an important role in excluding SWI/SNF from chromatin. Consistently, PRC1 compositions with a higher propensity for condensate formation are more effective in preventing SWI/SNF binding. Conversely, SWI/SNF-bound chromatin significantly reduces PRC1 binding and subsequent condensate formation. Notably, SWI/SNF can suppress PRC1 condensate formation in an ATP-hydrolysis independent manner. We propose that the condensate properties of different PRC1 compositions drive mutual PRC1-SWI/SNF antagonism to properly balance these competing regulatory activities during development.

biophysics↗

bioRxiv2023

Modularity of PRC1 Composition and Chromatin Interaction define Condensate Properties

Polycomb repressive complexes (PRC) play a key role in gene repression and are indispensable for proper development. Canonical PRC1 forms condensates in vitro and in cells and the ability of PRC1 to form condensates has been proposed to contribute to maintenance of repression. However, how chromatin and the various subunits of PRC1 contribute to condensation is largely unexplored. Using single-molecule imaging, we demonstrate that nucleosomal arrays and PRC1 act synergistically, reducing the critical concentration required for condensation by more than 20-fold. By reconstituting and imaging PRC1 with various subunit compositions, we find that the exact combination of PHC and CBX subunits determine the initiation, morphology, stability, and dynamics of condensates. In particular, the polymerization activity of PHC2 strongly influences condensate dynamics to promote formation of structures with distinct domains that adhere to each other but do not coalesce. Using live cell imaging, we confirmed that CBX properties are critical for condensate initiation and that PHC polymerization is important to maintain stable condensates. Together, we propose that PRC1 can fine-tune the degree and type of condensation by altering its composition which might offer important flexibility of regulatory function during different stages of development.

molecular biology↗

bioRxiv2018

Phase separation and nucleosome compaction are governed by the same domain of Polycomb Repressive Complex 1

Mammalian development requires effective mechanisms to repress genes whose expression would generate inappropriately specified cells. The Polycomb Repressive Complex 1 (PRC1) family complexes are central to maintaining this repression1. These include a set of canonical PRC1 complexes that each contain four core proteins, including one from the CBX family. These complexes have previously been shown to reside in membraneless organelles called Polycomb bodies, leading to speculation that canonical PRC1 might be found in a separate phase from the rest of the nucleus2,3. We show here that reconstituted PRC1 readily phase separates into droplets in vitro at low concentrations and physiological salt conditions. This behavior is driven by the CBX2 subunit. Point mutations in an internal domain of CBX2 eliminate phase separation. These same point mutations eliminate the formation of puncta in cells, and have previously been shown to eliminate nucleosome compaction in vitro4 and to generate axial patterning defects in mice5. Thus, a single domain in CBX2 is required for phase separation and nucleosome compaction, a finding that relates these functions to each other and to proper development.

molecular biology↗