Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein.

By A. Kuzmichev, K. Nishioka, H. Erdjument‐Bromage, Paul Tempst, D. Reinberg. Genes & Development, 2002

1,717 citations recorded by the source corpus.

Enhancer of Zeste [E(z)] is a Polycomb-group transcriptional repressor and one of the founding members of the family of SET domain-containing proteins. Several SET-domain proteins possess intrinsic histone methyltransferase (HMT) activity. However, recombinant E(z) protein was found to be inactive in a HMT assay. Here we report the isolation of a multiprotein E(z) complex that contains extra sex combs, suppressor of zeste-12 [Su(z)12], and the histone binding proteins RbAp46/RbAp48. This complex, which we termed Polycomb repressive complex (PRC) 2, possesses HMT activity with specificity for Lys 9 (K9) and Lys 27 (K27) of histone H3. The HMT activity of PRC2 is dependent on an intact SET domain in the E(z) protein. We hypothesize that transcriptional repression by the E(z) protein involves methylation-dependent recruitment of PRC1. The presence of Su(z)12, a strong suppressor of position effect variegation, in PRC2 suggests that PRC2 may play a widespread role in heterochromatin-mediated silencing.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/54db9246d49ce0ddc714b2d44e61a833d501696b

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Citations in the corpus

Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa (2010, background): “PRC2, which consists of Eed, Suz12 and Ezh2 or Ezh1, catalyzes trimethylation on histone H3 Lys27 (H3K27me3”
A model for transmission of the H3K27me3 epigenetic mark (2008, methodology): “The foci were identified using the “Nucleus Counter” in the ImageJ plug-in, which was set to (1) exclude regions below a size of 10 pixels, (2) to use a “maximum entropy threshold”, (3) use a “3x3 pixels median smoothing”, (4) use a “watershed algorithm” that divides neighbouring regions.”
Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. (2005, background): “…its mammalian counterpart EED-EZH2 complex possess H3-K27 methyltransferase activity (Beisel et al., 2002; Cao et al., 2002; Czermin et al., 2002; Kuzmichev et al., 2002; Milne et al., 2002; Muller et al., 2002; Nakamura et al., 2002), the PRC1 complex has been recently demonstrated to possess…”
The interplay of histone modifications – writers that read (2015, neutral): “For many modifications, it is not well established whether they directly influence transcription or their placement is simply a consequence of the transcriptional state present at a particular gene.”
Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. (2004, background): “Muller et al., 2002; Cao et al., 2002; Kuzmichev et al., 2002; Fischle et al., 2003; Min et al., 2003).”
Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put (2013, background): “A signature activity of PRC2 is methylation of histone H3 on K27 (Cao et al., 2002; Czermin et al., 2002; Kuzmichev et al., 2002; Müller et al., 2002).”
Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity (2004, background): “SUZ12, together with EZH2, EED and RbAp46/48, forms a complex, which has been shown to contain intrinsic K9/K27 HMT activity (Cao et al, 2002; Czermin et al, 2002; Kuzmichev et al, 2002; Muller et al, 2002).”
Poised chromatin at the ZEB1 promoter enables cell plasticity and enhances tumorigenicity (2013, neutral): “In contrast, trimethylation of lysine 27 (H3K27me3) is often associated with transcriptional repression mediated by the Polycomb group of proteins (Cao et al., 2002; Czermin et al., 2002; Kuzmichev et al., 2002; Muller et al., 2002).”
Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. (2003, background): “Several SET-domain histone lysine methyltransferases have been identified (Zhang and Reinberg 2001; Lachner and Jenuwein 2002): They methylate various lysine residues located at the flexible N termini of histones H3 and H4.”
Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms (2008, background): “Of note, HPC and its mammalian homologs contain a chromodomain that specifically binds the product of PRC2 catalysis, H3K27me2/3 (Bernstein et al., 2006; Kuzmichev et al., 2002; Wang et al., 2004b).”