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Title: Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes

Abstract

Epigenetic regulation is mediated by protein complexes that couple recognition of chromatin marks to activity or recruitment of chromatin-modifying enzymes. Polycomb repressive complex 2 (PRC2), a gene silencer that methylates lysine 27 of histone H3, is stimulated upon recognition of its own catalytic product and has been shown to be more active on dinucleosomes than H3 tails or single nucleosomes. These properties probably facilitate local H3K27me2/3 spreading, causing heterochromatin formation and gene repression. Here, cryo-EM reconstructions of human PRC2 bound to bifunctional dinucleosomes show how a single PRC2, via interactions with nucleosomal DNA, positions the H3 tails of the activating and substrate nucleosome to interact with the EED subunit and the SET domain of EZH2, respectively. We show how the geometry of the PRC2–DNA interactions allows PRC2 to accommodate varying lengths of the linker DNA between nucleosomes. Our structures illustrate how an epigenetic regulator engages with a complex chromatin substrate.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [2]
  1. Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biology (QB3); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrative Bio-Imaging Div.
  2. Univ. of California, Berkeley, CA (United States). California Inst. for Quantitative Biology (QB3), Howard Hughes Medical Inst., and Dept. of Molecular and Cell Biology; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics and Integrative Bio-Imaging Div.
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory-National Energy Research Scientific Computing Center
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1490278
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature Structural & Molecular Biology
Additional Journal Information:
Journal Volume: 25; Journal Issue: 2; Journal ID: ISSN 1545-9993
Country of Publication:
United States
Language:
English

Citation Formats

Poepsel, Simon, Kasinath, Vignesh, and Nogales, Eva. Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. United States: N. p., 2018. Web. doi:10.1038/s41594-018-0023-y.
Poepsel, Simon, Kasinath, Vignesh, & Nogales, Eva. Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. United States. doi:10.1038/s41594-018-0023-y.
Poepsel, Simon, Kasinath, Vignesh, and Nogales, Eva. Mon . "Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes". United States. doi:10.1038/s41594-018-0023-y. https://www.osti.gov/servlets/purl/1490278.
@article{osti_1490278,
title = {Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes},
author = {Poepsel, Simon and Kasinath, Vignesh and Nogales, Eva},
abstractNote = {Epigenetic regulation is mediated by protein complexes that couple recognition of chromatin marks to activity or recruitment of chromatin-modifying enzymes. Polycomb repressive complex 2 (PRC2), a gene silencer that methylates lysine 27 of histone H3, is stimulated upon recognition of its own catalytic product and has been shown to be more active on dinucleosomes than H3 tails or single nucleosomes. These properties probably facilitate local H3K27me2/3 spreading, causing heterochromatin formation and gene repression. Here, cryo-EM reconstructions of human PRC2 bound to bifunctional dinucleosomes show how a single PRC2, via interactions with nucleosomal DNA, positions the H3 tails of the activating and substrate nucleosome to interact with the EED subunit and the SET domain of EZH2, respectively. We show how the geometry of the PRC2–DNA interactions allows PRC2 to accommodate varying lengths of the linker DNA between nucleosomes. Our structures illustrate how an epigenetic regulator engages with a complex chromatin substrate.},
doi = {10.1038/s41594-018-0023-y},
journal = {Nature Structural & Molecular Biology},
number = 2,
volume = 25,
place = {United States},
year = {2018},
month = {1}
}

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Works referenced in this record:

The SANT domain: a unique histone-tail-binding module?
journal, February 2004

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