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Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation

Kuzmichev, Andrei, Margueron, Raphael, Vaquero, Alejandro, Preissner, Tanja S., Scher, Michael, Kirmizis, Antonis, Ouyang, Xuesong, Brockdorff, Neil, Abate-Shen, Cory, Farnham, Peggy, Reinberg, Danny·2005·Proceedings of the National Academy of Sciences

Abstract

Changes in the substrate specificities of factors that irreversibly modify the histone components of chromatin are expected to have a profound effect on gene expression through epigenetics. Ezh2 is a histone-lysine methyltransferase with activity dependent on its association with other components of the Polycomb Repressive Complexes 2 and 3 (PRC2/3). Ezh2 levels are increasingly elevated during prostate cancer progression. Other PRC2/3 components also are elevated in cancer cells. Overexpression of Ezh2 in tissue culture promotes formation of a previously undescribed PRC complex, PRC4, that contains the NAD + -dependent histone deacetylase SirT1 and isoform 2 of the PRC component Eed. Eed2 is expressed in cancer and undifferentiated embryonic stem (ES) cells but is undetectable in normal and differentiated ES cells. The distinct PRCs exhibit differential histone substrate specificities. These findings suggest that formation of a transformation-specific PRC complex may have a major role in resetting patterns of gene expression by regulating chromatin structure.

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Metadata

Authors
Kuzmichev, A., Margueron, R., Vaquero, A., Preissner, T. S., Scher, M., Kirmizis, A., Ouyang, X., Brockdorff, N., Abate-Shen, C., Farnham, P., & Reinberg, D.
Affiliations
Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, and Center for Advanced Biotechnology and Medicine, Department of Medicine and Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854; X Inactivation Group Medical Research Council Clinical Sciences Centre, Imperial College School of Medicine Hammersmith Hospital, London W12 0NN, United Kingdom; and McArdle Laboratory for Cancer Research, University of Wisconsin...
Venue
Proceedings of the National Academy of Sciences
Published
2005-01-31
Volume
102
Issue
6
Pages
1859-1864
ISSN
  • 0027-8424
  • 1091-6490
Cited by
336
References
4
Language
en

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Kuzmichev, A., Margueron, R., Vaquero, A., Preissner, T. S., Scher, M., Kirmizis, A., Ouyang, X., Brockdorff, N., Abate-Shen, C., Farnham, P., & Reinberg, D. (2005). Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0409875102