Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.

Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repre...

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Main Authors: Goedele N Maertens, Selma El Messaoudi-Aubert, Tomas Racek, Julie K Stock, James Nicholls, Marc Rodriguez-Niedenführ, Jesus Gil, Gordon Peters
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-07-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2713427?pdf=render
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author Goedele N Maertens
Selma El Messaoudi-Aubert
Tomas Racek
Julie K Stock
James Nicholls
Marc Rodriguez-Niedenführ
Jesus Gil
Gordon Peters
author_facet Goedele N Maertens
Selma El Messaoudi-Aubert
Tomas Racek
Julie K Stock
James Nicholls
Marc Rodriguez-Niedenführ
Jesus Gil
Gordon Peters
author_sort Goedele N Maertens
collection DOAJ
description Misexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families. In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest. Sequential chromatin immunoprecipitation (ChIP) reveals that CBX7 and CBX8 bind simultaneously to the same region of chromatin and knockdown of one of the Pc or Psc proteins results in release of the other, suggesting that the binding of PRC1 complexes is interdependent. Our findings provide the first evidence that a single gene can be regulated by several distinct PRC1 complexes and raise important questions about their configuration and relative functions.
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spelling doaj.art-c8fee45a47a84dd9ac42b4409c63fa8a2022-12-22T01:24:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-07-0147e638010.1371/journal.pone.0006380Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.Goedele N MaertensSelma El Messaoudi-AubertTomas RacekJulie K StockJames NichollsMarc Rodriguez-NiedenführJesus GilGordon PetersMisexpression of Polycomb repressive complex 1 (PRC1) components in human cells profoundly influences the onset of cellular senescence by modulating transcription of the INK4a tumor suppressor gene. Using tandem affinity purification, we find that CBX7 and CBX8, two Polycomb (Pc) homologs that repress INK4a, both participate in PRC1-like complexes with at least two Posterior sex combs (Psc) proteins, MEL18 and BMI1. Each complex contains a single representative of the Pc and Psc families. In primary human fibroblasts, CBX7, CBX8, MEL18 and BMI1 are present at the INK4a locus and shRNA-mediated knockdown of any one of these components results in de-repression of INK4a and proliferative arrest. Sequential chromatin immunoprecipitation (ChIP) reveals that CBX7 and CBX8 bind simultaneously to the same region of chromatin and knockdown of one of the Pc or Psc proteins results in release of the other, suggesting that the binding of PRC1 complexes is interdependent. Our findings provide the first evidence that a single gene can be regulated by several distinct PRC1 complexes and raise important questions about their configuration and relative functions.http://europepmc.org/articles/PMC2713427?pdf=render
spellingShingle Goedele N Maertens
Selma El Messaoudi-Aubert
Tomas Racek
Julie K Stock
James Nicholls
Marc Rodriguez-Niedenführ
Jesus Gil
Gordon Peters
Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
PLoS ONE
title Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
title_full Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
title_fullStr Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
title_full_unstemmed Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
title_short Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
title_sort several distinct polycomb complexes regulate and co localize on the ink4a tumor suppressor locus
url http://europepmc.org/articles/PMC2713427?pdf=render
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