Chromatin topology is coupled to Polycomb group protein subnuclear organization

• Published in: Nature communications Vol. 7; no. 1; pp. 10291 - 13
• Main Authors: Wani, Ajazul H., Boettiger, Alistair N., Schorderet, Patrick, Ergun, Ayla, Münger, Christine, Sadreyev, Ruslan I., Zhuang, Xiaowei, Kingston, Robert E., Francis, Nicole J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.01.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/63; 38/15; 38/39; 631/337/100/101; 631/80/86; Amino Acid Motifs; Animals; Biology; Cell Line; Chromatin - metabolism; Chromatin Immunoprecipitation; DNA-Binding Proteins - metabolism; Drosophila; Drosophila Proteins - metabolism; Fluorescent Antibody Technique; Gene expression; Genomes; Humanities and Social Sciences; Insects; Intranuclear Space - metabolism; Microscopy; Molecular Dynamics Simulation; multidisciplinary; Optical Imaging; Polycomb Repressive Complex 1 - metabolism; Polycomb-Group Proteins - metabolism; Polymerization; Polymers; Protein Structure, Quaternary; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Science; Science (multidisciplinary); Sequence Analysis, DNA; Sequence Analysis, RNA; Topology; Canada; United States > US; Massachusetts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10291

The genomes of metazoa are organized at multiple scales. Many proteins that regulate genome architecture, including Polycomb group (PcG) proteins, form subnuclear structures. Deciphering mechanistic links between protein organization and chromatin architecture requires precise description and mechanistic perturbations of both. Using super-resolution microscopy, here we show that PcG proteins are organized into hundreds of nanoscale protein clusters. We manipulated PcG clusters by disrupting the polymerization activity of the sterile alpha motif (SAM) of the PcG protein Polyhomeotic (Ph) or by increasing Ph levels. Ph with mutant SAM disrupts clustering of endogenous PcG complexes and chromatin interactions while elevating Ph level increases cluster number and chromatin interactions. These effects can be captured by molecular simulations based on a previously described chromatin polymer model. Both perturbations also alter gene expression. Organization of PcG proteins into small, abundant clusters on chromatin through Ph SAM polymerization activity may shape genome architecture through chromatin interactions. Polycomb Group (PcG) proteins regulate gene expression and genome architecture. Using super-resolution microscopy and molecular simulations, Wani et al . describe the organization of PcG proteins into hundreds of nano-scale protein clusters and suggest these clusters shape genome architecture.