Role of histone H2A ubiquitination in Polycomb silencing

  title={Role of histone H2A ubiquitination in Polycomb silencing},
  author={Hengbin Wang and Liangjun Wang and Hediye Erdjument-Bromage and Miguel Vidal and Paul Tempst and Richard S. Jones and Yi Zhang},
Covalent modification of histones is important in regulating chromatin dynamics and transcription. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination and a ‘cross-talk’ between H2B ubiquitination and histone methylation, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization… 

Transcriptional activation of polycomb-repressed genes by ZRF1

It is shown in human cell lines that ZRF1 (zuotin-related factor 1) is specifically recruited to histone H2A when it is ubiquitinated at Lys 119 by means of a novel ubiquitin-interacting domain that is located in the evolutionarily conserved zuotin domain.

dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing.

A novel mode of histone crosstalk during gene silencing is described, in which histone H2A monoubiquitylation is coupled to the removal of hist one H3 Lys 36 dimethylation (H3K36me2).

Regulation of cell cycle progression and gene expression by H2A deubiquitination

It is demonstrated that H2A deubiquitinase is critically involved in cell cycle progression and gene expression and that blocking the function of Ubp-M results in defective posterior development in Xenopus laevis.

Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing

The identification of RSF1 (remodeling and spacing factor 1), a subunit of the RSF complex, as a H2Aub binding protein, which mediates the gene-silencing function of this histone modification is reported.

Role of Bmi1 in H2A Ubiquitylation and Hox Gene Silencing*

It is reported here that the oncogene Bmi 1 stimulates H2A ubiquitylation both in vitro and in vivo and that Bmi1-regulated H2C5 gene expression in vivo is required for Hox gene silencing and normal cell growth.

The role and regulation of histone H2B monoubiquitination during tumorigenesis

It was demonstrated that H2Bub1 depletion could be rescued through knockdown of various subunits of the deubiquitinating module of the SAGA complex and presented data which support the hypothesis that the RNF20/RNF40 complex has a tumor-suppressor function probably through its regulation of H2 Bub1.

Writing Histone Monoubiquitination in Human Malignancy—The Role of RING Finger E3 Ubiquitin Ligases

A review of a number of sites and the E3 RING finger ubiquitin ligases that write them that are associated with transcriptional elongation and DNA damage response and a key epigenomic event shaping the chromatin landscape of malignancy and influencing how cells respond to DNA damage.



Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast

It is shown that the ubiquitin-conjugating enzyme Rad6 (Ubc2) mediates methylation of histone H3 at lysine 4 (Lys 4) through ubiquitination of H2B at Lys 123 in yeast (Saccharomyces cerevisiae) to reveal a pathway leading to gene regulation through concerted histone modifications on distinct histone tails.

Rad6 plays a role in transcriptional activation through ubiquitylation of histone H2B.

The data suggest that Rad6 and SAGA function independently during galactose induction, and that the staged recruitment of these two factors to the GAL1 promoter regulates the ubiquitylation and deubiquitylation of H2B.

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

The purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex, is reported, and it is demonstrated that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27).

Gene silencing: Trans-histone regulatory pathway in chromatin

It is suggested that H2B ubiquitination acts as a master switch that controls the site-selective histone methylation patterns responsible for this silencing.

Ubiquitination of Histone H2B by Rad6 Is Required for Efficient Dot1-mediated Methylation of Histone H3 Lysine 79*

It is shown that Rad6-mediated ubiquitination of H2B lysine 123 is important for efficient methylation of lysin 79, but not lysines 36, of histone H3, and this study suggests that Rad 6 affects telomeric silencing, at least in part, by influencingmethylation of hist one H3.

Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8.

The results suggest that the histone H2B ubiquitylation state is dynamic during transcription, and that the sequence of histone modifications helps to control transcription.

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.

Methylation of Histone H3 by COMPASS Requires Ubiquitination of Histone H2B by Rad6*

The genome of the yeast Saccharomyces cerevisiae was surveyed for genes necessary for histone methylation, and it was discovered that the ubiquitin-conjugating enzyme Rad6 is required for methylation of lysine 4 of histone H3.

Structure of polyubiquitinated histone H2A.

The results suggest that the major arrangement of Ubiquitin in polyubiquitinated H2A is a chain of ubiquitin molecules joined to each other by isopeptide bonds to a ubiquit in molecule that is attached to the epsilon-amino group of lysine 119 of histone H 2A.