Disease relevance of Ezh2

• Ezh2 levels are increasingly elevated during prostate cancer progression [1].
• We observed that Ezh2 binds to pRb2/p130, a member of the retinoblastoma family; as such, we were led to consider the possible ability of Ezh2 to modulate cell cycle progression [2].

High impact information on Ezh2

• Revealed function of Ezh2 points to a broader usage of lysine methylation in regulation of both nuclear and extra-nuclear signaling processes [3].
• Genetic evidence supports the essential role of cytosolic Ezh2 in actin polymerization-dependent processes such as antigen receptor signaling in T cells and PDGF-induced dorsal circular ruffle formation in fibroblasts [3].
• Eed-Ezh2 Polycomb complexes are recruited to the paternal chromosome and potentially regulate its repressive histone methylation [4].
• The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation [5].
• In undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1 [5].

Biological context of Ezh2

• The early lethal phenotype is reminiscent of that of the PcG-gene knockouts Eed and Ezh2, which belong to a separate functional PcG group and PcG protein complex [6].
• This accumulation and the associated histone methylation are also lost in Ezh2 mutants, suggesting a role in X inactivation [7].
• By contrast, in the differentiating trophectoderm cells where Oct4 expression is progressively downregulated Ezh2/Eed complex is recruited transiently to one X chromosome in female embryos at the onset of X-inactivation [7].
• Enhancer of zeste 2 (Ezh2), a SET domain-containing protein, is crucial for development in many model organisms, including early mouse development [7].
• This phenotypic effect on growth could be attributed to the asymmetric localisation of the Ezh2/Eed complex and the associated histone methylation pattern to the maternal genome, which is disrupted in Ezh2 mutant zygotes [7].

Anatomical context of Ezh2

• We have used a conditional allele of Ezh2 to deplete the oocyte of this maternal inheritance [7].
• Trimethylation of histone H3 on lysine 27, mediated by a PcG protein complex consisting of Eed, Ezh2, and Suz12, is integral in differentiation, stem cell self-renewal, and tumorigenesis [8].
• Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells [9].
• We report that Ezh2 expression was developmentally regulated in the myotome compartment of mouse somites and that its down-regulation coincided with activation of muscle gene expression and differentiation of satellite-cell-derived myoblasts [5].
• We also revealed Ezh2 as a key regulator of histone H3 methylation in early B cell progenitors [10].

Associations of Ezh2 with chemical compounds

• Quiescent B cells also lacked heterochromatin-associated HP1beta and Ikaros at pericentric chromatin and expressed low levels of Ezh2 and ESET histone methyl transferases (HMTases) [11].

Physical interactions of Ezh2

• The association of Eed/Enx1 complexes is mitotically stable, suggesting a mechanism for the maintenance of imprinted X inactivation in these cells [9].

Regulatory relationships of Ezh2

• Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement [10].

Other interactions of Ezh2

• Therefore, STAT5 functions at a distinct step in regulating distal V(H) recombination in relation to the transcription factor Pax5 and histone methyltransferase Ezh2 [12].
• Here we show that Eed and a second Polycomb group protein, Enx1, are directly localized to the inactive X chromosome in XX trophoblast stem (TS) cells [9].
• The murine polycomb-group genes Ezh1 and Ezh2 map close to Hox gene clusters on mouse chromosomes 11 and 6 [13].
• Our data suggest Ezh2-dependent histone H3 methylation as a novel regulatory mechanism controlling Igh rearrangement during early murine B cell development [10].
• The expression profile of the newly produced CD41+ cells showed high levels of transcripts encoding Ezh2, TdT, Rag2, and various immunoglobulin (Ig) heavy chains [14].

Analytical, diagnostic and therapeutic context of Ezh2

• More importantly, whereas normal HSCs were rapidly exhausted after serial transplantations, overexpression of Ezh2 completely conserved long-term repopulating potential [15].

References