Different Ezh2-containing complexes target methylation of histone H1 or nucleosomal histone H3 Journal Article

Authors: Kuzmichev, A.; Jenuwein, T.; Tempst, P.; Reinberg, D.
Article Title: Different Ezh2-containing complexes target methylation of histone H1 or nucleosomal histone H3
Abstract: Human Enhancer of Zeste homolog (Ezh2) is a histone lysine methyltransferase (HKMT) associated with transcriptional repression. Ezh2 is present in several distinct complexes, one of which, PRC2, we characterized previously. Here we report an additional Ezh2 complex, PRC3. We show that the Ezh2 complexes exhibit differential targeting of specific histones for lysine methylation dependent upon the context of the histone substrates. This differential targeting is a function of the associated Eed protein within each complex. We found that Eed protein is present in four isoforms, which represent alternate translation start site usage from the same mRNA. These Eed isoforms selectively associate with distinct Ezh2-containing complexes with resultant differential targeting of their associated HKMT activity toward histone H3-K27 or histone H1-K26. Our data provide evidence for a novel mechanism regulating the substrate specificity of a chromatin-modifying enzyme through disparate translational products of a regulatory subunit.
Keywords: controlled study; unclassified drug; human cell; methylation; dna-binding proteins; proteins; gene targeting; models, biological; embryo; protein targeting; protein; enzyme activity; hela cells; genetic vectors; transcription factors; molecular mechanics; blotting, western; antibodies, monoclonal; methyltransferase; methyltransferases; protein processing, post-translational; messenger rna; rna, messenger; chromatin; histone h3; recombinant proteins; substrate specificity; binding sites; genes, reporter; protein subunit; point mutation; enzyme specificity; repressor proteins; histones; isoprotein; protein isoforms; lysine; electrophoresis, polyacrylamide gel; enzyme; gene expression regulation, enzymologic; nucleosome; nucleosomes; histone lysine methyltransferase; embryonic ectoderm development protein; histone h1; precipitin tests; humans; human; article; human enhancer of zeste homolog; polycomb repressive complex
Journal Title: Molecular Cell
Volume: 14
Issue: 2
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2004-04-23
Start Page: 183
End Page: 193
Language: English
DOI: 10.1016/s1097-2765(04)00185-6
PROVIDER: scopus
PUBMED: 15099518
Notes: Mol. Cell -- Cited By (since 1996):263 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Source: Scopus
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  1. Paul J Tempst
    312 Tempst