Topology and enzymatic properties of a canonical Polycomb repressive complex 1 isoform.
Matteo ColomboOmbeline PesseyMarco MarciaPublished in: FEBS letters (2019)
Polycomb repressive complex 1 (PRC1) catalyses monoubiquitination of histone H2A on Lys119, promoting gene silencing. Cells at different developmental stages and in different tissues express different PRC1 isoforms. The topology, subunit composition, structural architecture and molecular mechanism of most of these isoforms are still poorly characterized. Here, we have purified a PRC1 isoform comprising subunits RING1B, PCGF2, CBX2 and PHC2, two stable subcomplexes (RING1B-PCGF2 and RING1B-PHC2) and the catalytic subunit RING1B in isolation. By crosslinking mass spectrometry, we identified novel interactions between RING1B and the three non-catalytic subunits. Biochemical, biophysical, and enzymatic data suggest that CBX2 and PHC2 play a structural role, whereas PCGF2 also modulates catalysis. Our data offer insights into the molecular architecture of PRC1 and its histone ubiquitination activity.
Keyphrases
- mass spectrometry
- electronic health record
- hydrogen peroxide
- induced apoptosis
- gene expression
- high resolution
- cell cycle arrest
- oxidative stress
- liquid chromatography
- nitric oxide
- machine learning
- protein kinase
- cell proliferation
- high performance liquid chromatography
- single molecule
- cell death
- gas chromatography
- deep learning
- artificial intelligence