Molecular architecture of human polycomb repressive complex 2
Claudio Ciferri,
Gabriel C Lander,
Alessio Maiolica,
Franz Herzog,
Ruedi Aebersold,
Eva Nogales
Affiliations
Claudio Ciferri
Department of Molecular and Cell Biology, University of California, Berkeley, United States
Gabriel C Lander
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States
Alessio Maiolica
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
Franz Herzog
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
Ruedi Aebersold
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland; Faculty of Science, University of Zurich, Zurich, Switzerland
Eva Nogales
Department of Molecular and Cell Biology, University of California, Berkeley, United States; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, United States; Howard Hughes Medical Institute, UC Berkeley, Berkeley, United States
Polycomb Repressive Complex 2 (PRC2) is essential for gene silencing, establishing transcriptional repression of specific genes by tri-methylating Lysine 27 of histone H3, a process mediated by cofactors such as AEBP2. In spite of its biological importance, little is known about PRC2 architecture and subunit organization. Here, we present the first three-dimensional electron microscopy structure of the human PRC2 complex bound to its cofactor AEBP2. Using a novel internal protein tagging-method, in combination with isotopic chemical cross-linking and mass spectrometry, we have localized all the PRC2 subunits and their functional domains and generated a detailed map of interactions. The position and stabilization effect of AEBP2 suggests an allosteric role of this cofactor in regulating gene silencing. Regions in PRC2 that interact with modified histone tails are localized near the methyltransferase site, suggesting a molecular mechanism for the chromatin-based regulation of PRC2 activity.
