Article ; Online: Chromatin topology is coupled to Polycomb group protein subnuclear organization.
2016 Volume 7, Page(s) 10291
Abstract: ... links between protein organization and chromatin architecture requires precise description and ... architecture, including Polycomb group (PcG) proteins, form subnuclear structures. Deciphering mechanistic ... gene expression. Organization of PcG proteins into small, abundant clusters on chromatin through Ph SAM ...
| Abstract | 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. |
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| MeSH term(s) | Amino Acid Motifs ; Animals ; Cell Line ; Chromatin/metabolism ; Chromatin Immunoprecipitation ; DNA-Binding Proteins/metabolism ; Drosophila ; Drosophila Proteins/metabolism ; Fluorescent Antibody Technique ; Intranuclear Space/metabolism ; Microscopy ; Molecular Dynamics Simulation ; Optical Imaging ; Polycomb Repressive Complex 1/metabolism ; Polycomb-Group Proteins/metabolism ; Polymers ; Protein Structure, Quaternary ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Analysis, RNA |
| Chemical Substances | Chromatin ; DNA-Binding Proteins ; Drosophila Proteins ; Polycomb-Group Proteins ; Polymers ; ph-d protein, Drosophila ; Polycomb Repressive Complex 1 (EC 2.3.2.27) |
| Language | English |
| Publishing date | 2016-01-13 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/ncomms10291 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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