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Science. 2018 Feb 23;359(6378):940-944. doi: 10.1126/science.aar5700. Epub 2018 Jan 18.

Structures of human PRC2 with its cofactors AEBP2 and JARID2.

Author information

1
QB3 Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
2
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
3
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland.
4
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
5
Faculty of Science, University of Zurich, Zurich, Switzerland.
6
QB3 Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. enogales@lbl.gov.
7
Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.

Abstract

Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.

PMID:
29348366
PMCID:
PMC5840869
DOI:
10.1126/science.aar5700
[Indexed for MEDLINE]
Free PMC Article

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