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

Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1859-64. doi: 10.1073/pnas.0409875102.

Andrei Kuzmichev ¹, Raphael Margueron, Alejandro Vaquero, Tanja S Preissner, Michael Scher, Antonis Kirmizis, Xuesong Ouyang, Neil Brockdorff, Cory Abate-Shen, Peggy Farnham, Danny Reinberg

Affiliations

Affiliation

1 Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

PMID: 15684044 DOI: 10.1073/pnas.0409875102

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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