Crossref journal-article
eLife Sciences Publications, Ltd
eLife (4374)
Abstract

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.

Bibliography

Ciferri, C., Lander, G. C., Maiolica, A., Herzog, F., Aebersold, R., & Nogales, E. (2012). Molecular architecture of human polycomb repressive complex 2. ELife, 1. CLOCKSS.

Authors 6
  1. Claudio Ciferri (first)
  2. Gabriel C Lander (additional)
  3. Alessio Maiolica (additional)
  4. Franz Herzog (additional)
  5. Ruedi Aebersold (additional)
  6. Eva Nogales (additional)
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Dates
Type When
Created 12 years, 9 months ago (Oct. 30, 2012, 12:41 a.m.)
Deposited 1 year, 10 months ago (Oct. 11, 2023, 8:37 p.m.)
Indexed 3 weeks ago (July 30, 2025, 1:07 p.m.)
Issued 12 years, 9 months ago (Oct. 30, 2012)
Published 12 years, 9 months ago (Oct. 30, 2012)
Published Online 12 years, 9 months ago (Oct. 30, 2012)
Funders 14
  1. NIGMS 10.13039/100000057 National Institute of General Medical Sciences

    Region: Americas

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    1. U.S. National Institute of General Medical Sciences
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    Awards1
    1. HEALTH-F4-2008-201648
  3. ERC advanced grant “Proteomics v3.0”
    Awards1
    1. 233226
  4. Damon Runyon Cancer Research Foundation Fellowship
  5. Marie Curie Fellowship
  6. EMBO Fellowship
  7. Howard Hughes Medical Institute 10.13039/100000011

    Region: Americas

    pri (Research institutes and centers)

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    1. Howard Hughes Medical Institute Inc
    2. HHMI
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    gov (National government)

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    1. U.S. National Institute of General Medical Sciences
    2. NIGMS
    Awards1
    1. GM63072
  9. European Union Seventh Framework Program PROSPECTS
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    1. HEALTH-F4-2008-201648
  10. European Research Council 10.13039/501100000781

    Region: Europe

    gov (National government)

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    1. ERC
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    1. 233226
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    gov (Trusts, charities, foundations (both public and private))

    Labels4
    1. Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation
    2. Damon Runyon
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  13. EMBO 10.13039/501100003043
  14. Howard Hughes Medical Institute 10.13039/100000011

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@article{Ciferri_2012, title={Molecular architecture of human polycomb repressive complex 2}, volume={1}, ISSN={2050-084X}, url={http://dx.doi.org/10.7554/elife.00005}, DOI={10.7554/elife.00005}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Ciferri, Claudio and Lander, Gabriel C and Maiolica, Alessio and Herzog, Franz and Aebersold, Ruedi and Nogales, Eva}, year={2012}, month=oct }