Abstract
Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Carrier Proteins / isolation & purification
-
Carrier Proteins / metabolism
-
Cell Cycle Proteins / metabolism
-
Chromatin / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Drosophila
-
Drosophila Proteins / genetics
-
Drosophila Proteins / metabolism*
-
Enhancer of Zeste Homolog 2 Protein
-
Gene Silencing*
-
Genes, Homeobox
-
HeLa Cells
-
Histone Methyltransferases
-
Histone-Lysine N-Methyltransferase*
-
Histones / metabolism*
-
Homeodomain Proteins*
-
Humans
-
Lysine / metabolism*
-
Methylation
-
Methyltransferases / isolation & purification
-
Methyltransferases / metabolism
-
Nuclear Proteins / metabolism
-
Nucleosomes / metabolism
-
Peptide Mapping
-
Polycomb Repressive Complex 1
-
Polycomb Repressive Complex 2
-
Precipitin Tests
-
Protein Methyltransferases
-
Proteins / isolation & purification
-
Proteins / metabolism
-
RNA Interference
-
Repressor Proteins / isolation & purification
-
Repressor Proteins / metabolism
-
Response Elements
-
Temperature
-
Transcription Factors*
Substances
-
Carrier Proteins
-
Cell Cycle Proteins
-
Chromatin
-
DNA-Binding Proteins
-
Drosophila Proteins
-
EED protein, human
-
Histones
-
Homeodomain Proteins
-
Nuclear Proteins
-
Nucleosomes
-
PRC1 protein, human
-
Pc protein, Drosophila
-
Proteins
-
Repressor Proteins
-
Transcription Factors
-
Ubx protein, Drosophila
-
Histone Methyltransferases
-
Methyltransferases
-
Protein Methyltransferases
-
E(z) protein, Drosophila
-
EZH2 protein, human
-
Enhancer of Zeste Homolog 2 Protein
-
Histone-Lysine N-Methyltransferase
-
Polycomb Repressive Complex 2
-
esc protein, Drosophila
-
Polycomb Repressive Complex 1
-
Lysine