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

  title={Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing},
  author={Ru Cao and Liangjun Wang and Hengbin Wang and Li Xia and Hediye Erdjument-Bromage and Paul Tempst and Richard S. Jones and Yi Zhang},
  pages={1039 - 1043}
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 theDrosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3… 

Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27.

It is shown that HKMT-Ezh2 and Eed, two other components of the PRC2/3 complexes, colocalize to the target promoters with Suz 12, and recruitment of Suz12, Ezh2 andEed to target promoters coincides with methylation of histone H3 on Lys 27.

Role of Histone H3 Lysine 27 Methylation in X Inactivation

It is demonstrated that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation.

Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes

The methylation to acetylation switch correlates with the transcriptional activation of PcG target genes, both during ES cell differentiation and in MLL-AF9-transduced hematopoietic stem cells.

Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8

Functional analyses revealed that interactions between class 1 and class 2 PcG complexes play decisive roles in the maintenance of Hox gene repression outside their expression domain.

Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8

Functional analyses revealed that interactions between class 1 and class 2 PcG complexes play decisive roles in the maintenance of Hox gene repression outside their expression domain.

Substrate Preferences of the EZH2 Histone Methyltransferase Complex*

The hypothesis that linker histone H1 and chromatin structure are important factors in determining the substrate preference of the EZH2 histone methyltransferase complex is supported, which suggests that Embryonic Ectoderm Development EED isoforms may affect substrate specificity.

Polycomb Complexes and the Propagation of the Methylation Mark at the Drosophila Ubx Gene*

It is proposed that the Polycomb chromodomain is required for the looping mechanism that spreads methylation over a broad domain, which in turn is needed for the stability of thePolycomb group protein complex.

Dense Chromatin Activates Polycomb Repressive Complex 2 to Regulate H3 Lysine 27 Methylation

It is proposed that PRC2 can sense the chromatin environment to exert its role in the maintenance of transcriptional states, and activity is regulated by the density of its substrate nucleosome arrays.

Role of hPHF1 in H3K27 Methylation and Hox Gene Silencing

The results reveal hPHF1 as a component of a novel EED-EZH2 complex and demonstrate its important role in H3K27 methylation and Hox gene silencing.



Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins

It is shown that mammalian methyltransferases that selectively methylate histone H3 on lysine 9 (Suv39h HMTases) generate a binding site for HP1 proteins—a family of heterochromatic adaptor molecules implicated in both gene silencing and supra-nucleosomal chromatin structure.

Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation

It is shown that EED interacts, both in vitro and in vivo, with histone deacetylase (HDAC) proteins, which is highly specific because the HDAC proteins do not interact with other vertebrate PcG proteins.

Regulation of chromatin structure by site-specific histone H3 methyltransferases

A functional interdependence of site-specific H3 tail modifications is revealed and a dynamic mechanism for the regulation of higher-order chromatin is suggested.

Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain

A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.

Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.

It is reported that lysine (Lys) 79 of histone H3, which resides in the globular domain, is methylated in eukaryotic organisms and indicates that histone modifications in the core globulardomain have important biological functions.

General transcription factors bind promoters repressed by Polycomb group proteins

It is shown that binding of PcG proteins to repressed promoters does not exclude general transcription factors (GTFs) and that depletion of P cG proteins by double-stranded RNA interference leads to de-repression of developmentally regulated genes, and it is suggested that Pcg complexes maintain silencing by inhibiting GTF-mediated activation of transcription.

Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9

It is shown that HP1 uses an induced-fit mechanism for recognition of methylation of lysine 9 in histone H3, which predicts which other chromodomains will bind methylated proteins and suggest a motif that they recognize.

The Drosophila Polycomb Group proteins ESC and E(Z) are present in a complex containing the histone-binding protein p55 and the histone deacetylase RPD3.

It is reported here that ESC, together with E(Z), is present in a 600 kDa complex that is distinct from complexes containing other PcG proteins, and it is proposed that histone deacetylation by this complex is a prerequisite for establishment of stable long-term silencing by other continuously required P cG complexes.