Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing

2002/10/31 by Ru Cao, Liangjun Wang, Hengbin Wang +5 · 13 citations
Biochemistry, Genetics and Molecular Biology · #Biology #Cancer-related gene regulation #Cell biology #Chromodomain #DNA methylation #EZH2 #Epigenetics and DNA Methylation #Gene #Gene expression #Gene silencing #Genetics #Histone #Histone H2A #Histone H3 #Histone methylation #Histone methyltransferase #Methylation #PRC2 #Polycomb-group proteins #RNA #RNA modifications and cancer #Repressor

paper · doi:10.1126/science.1076997

openalex publication_date 2002/10/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05

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.

Citations

• Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
• Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
• The language of covalent histone modifications
• Regulation of chromatin structure by site-specific histone H3 methyltransferases

Cited by

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• Role of histone H2A ubiquitination in Polycomb silencing
• RYBP-PRC1 Complexes Mediate H2A Ubiquitylation at Polycomb Target Sites Independently of PRC2 and H3K27me3
• The landscape of histone modifications across 1% of the human genome in five human cell lines
• Controlling the double helix
• Protein post-translational modifications and regulation of pluripotency in human stem cells
• The winding path of protein methylation research: milestones and new frontiers
• DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby promotes H3K27 methylation
• The chromatin signature of pluripotent cells
• Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
• Histone methylation: a dynamic mark in health, disease and inheritance
• Histone [wikipedia]