@article{06ea8eeb3f0448d78963e7a9402cbd3f,
title = "Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding",
abstract = "Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120 kDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2, and Aebp2 fragments that is minimally active in nucleosome binding and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a non-canonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2. Suz12 and Aebp2 progressively block histone H3K4 binding to Rbbp4, suggesting that Rbbp4 may not be directly involved in PRC2 inhibition by the active H3K4me3 histone mark. Nucleosome binding enabled by Jarid2 and Aebp2 is in part accounted for by the structures, which also reveal that disruption of the Jarid2-Suz12 interaction may underlie the disease mechanism of an oncogenic chromosomal translocation of Suz12. Chen et al. solved the crystal structure of Suz12-Rbbp4-Jarid2-Aebp2 that provides important insights into PRC2 function and regulation, including the organization of PRC2 holo complexes, the binding of nucleosomes and histone tails, and a molecular consequence of an oncogenic chromosomal translocation of Suz12.",
keywords = "Aebp2, H3K27me3, Jarid2, PRC2, Polycomb repressive complex 2, Rbbp4, Suz12, chromatin complex, development, gene silencing, histone methylation",
author = "Siming Chen and Lianying Jiao and Murtada Shubbar and Xin Yang and Xin Liu",
note = "Funding Information: The cDNAs of human PRC2 subunits were kindly provided by Dr. Robert Kingston of the Harvard Medical School and Massachusetts General Hospital. This research was supported by Welch Foundation research grant I-1790 , CPRIT research grant R1119 , Rita Allen Foundation research grant, and NIH grants GM114576 and GM121662 to X.L. X.L. is a W.W. Caruth, Jr., Scholar in Biomedical Research . This research also received support from the Cecil H. and Ida Green Center Training Program in Reproductive Biology Sciences Research . This research used the Protein and Monoclonal Antibody Production Shared Resource of Baylor College of Medicine. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. DOE under contract no. DE-AC02-05CH11231. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under contract no. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences (including P41GM103393). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. The crystal structures described in this study have been deposited in the Protein Data Bank under accession numbers PDB: 5WAI and PDB: 5WAK . Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = mar,
day = "1",
doi = "10.1016/j.molcel.2018.01.039",
language = "English (US)",
volume = "69",
pages = "840--852.e5",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",
}