The Drosophila pleiohomeotic mutation enhances the Polycomblike and Polycomb mutant phenotypes during embryogenesis and in the adult

In Drosophila, the spatially restricted expression of the homeotic genes is controlled by Polycomb group (PcG) repression. PcG proteins appear to form different complexes to repress this gene expression. Although the pleiohomeotic gene (pho) shares mutational phenotypes with other PcG mutations, which demonstrates that PHO binds directly with a Polycomb (Pc)-containing complex, the genetic interactions of pho with other PcG genes have not been examined in detail. Here we investigated whether pho interacts with Polycomblike (Pcl) and Polycomb (Pc) during embryonic and adult development using developmental and genetic approaches. Pcl and Pc strongly enhanced pho phenotypes in the legs and tergite of the adult fly. Embryonic cuticle transformation was also greatly enhanced in Pcl; pho or Pc; pho double mutant embryos. The double mutant phenotypes were more severely affected by the pho maternal effect mutation than in zygotic mutant background, suggesting dosage-dependent processes. Taken together, these results provide genetic evidence of an interaction between PHO with other Polycomb group proteins at the embryonic and adult stages, and of the functioning of PHO as a component of the PcG complex.     

The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos

Polycomb group (PcG) proteins form multimeric protein complexes which are involved in the heritable stable repression of genes. Previously, we identified two distinct human PcG protein complexes. The EED-EZH protein complex contains the EED and EZH2 PcG proteins, and the HPC-HPH PcG complex contains the HPC, HPH, BMI1, and RING1 PcG proteins. Here we show that YY1, a homolog of the Drosophila PcG protein pleiohomeotic (Pho), interacts specificially with the human PcG protein EED but not with proteins of the HPC-HPH PcG complex. Since YY1 and Pho are DNA-binding proteins, the interaction between YY1 and EED provides a direct link between the chromatin-associated EED-EZH PcG complex and the DNA of target genes. To study the functional significance of the interaction, we expressed the Xenopus homologs of EED and YY1 in Xenopus embryos. Both Xeed and XYY1 induce an ectopic neural axis but do not induce mesodermal tissues. In contrast, members of the HPC-HPH PcG complex do not induce neural tissue. The exclusive, direct neuralizing activity of both the Xeed and XYY1 proteins underlines the significance of the interaction between the two proteins. Our data also indicate a role for chromatin-associated proteins, such as PcG proteins, in Xenopus neural induction.     

Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins

Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures.     

Polycomb group蛋白复合体

Polycomb group (PcG) 蛋白是一组通过染色质修饰调控靶基因的转录抑制子, 从生化和功能上它可以分成两个主要的核心蛋白复合体PRC1(Polycomb repressive complex 1)和PRC2(Polycomb repressive complex 2)。研究发现PcG蛋白不仅控制个体正确的发育模式, 而且与细胞的增殖、分化和肿瘤发生有关。文章就PcG蛋白的组成、作用机制及功能进行综述, 并对PcG未来的研究方向进行展望。     

BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair

Polycomb group (PcG) proteins are major determinants of cell identity, stem cell pluripotency, and epigenetic gene silencing during development. The polycomb repressive complex 1, which contains BMI1, RING1, and RING2, functions as an E3-ubuiquitin ligase. We found that BMI1 and RING2 are recruited to sites of DNA double-strand breaks (DSBs) where they contribute to the ubiquitylation of γ-H2AX. In the absence of BMI1, several proteins dependent on ubiquitin signaling, including 53BP1, BRCA1, and RAP80, are impaired in recruitment to DSBs. Loss of BMI1 sensitizes cells to ionizing radiation to the same extent as loss of RNF8. The simultaneous depletion of both proteins revealed an additive increase in radiation sensitivity. These data uncover an unexpected link between the polycomb and the DNA damage response pathways, and suggest a novel function for BMI1 in maintaining genomic stability.     

Enhancer of Polycomb is a suppressor of position-effect variegation in Drosophila melanogaster.

Polycomb group (PcG) genes of Drosophila are negative regulators of homeotic gene expression required for maintenance of determination. Sequence similarity between Polycomb and Su(var)205 led to the suggestion that PcG genes and modifiers of position-effect variegation (PEV) might function analogously in the establishment of chromatin structure. If PcG proteins participate directly in the same process that leads to PEV, PcG mutations should suppress PEV. We show that mutations in E(Pc), an unusual member of the PcG, suppress PEV of four variegating rearrangements: In(l)wm4, B(SV), T(2;3)Sb(V) and In(2R)bw(VDe2). Using reversion of a Pelement insertion, deficiency mapping, and recombination mapping as criteria, homeotic effects and suppression of PEV associated with E(Pc) co-map. Asx is an enhancer of PEV, whereas nine other PcG loci do not affect PEV. These results support the conclusion that there are fewer similarities between PcG genes and modifiers of PEV than previously supposed. However, E(Pc) appears to be an important link between the two groups. We discuss why Asx might act as an enhancer of PEV.     

Polycomb group and trithorax group proteins in Arabidopsis

Polycomb group (PcG) and trithorax group (trxG) proteins form molecular modules of a cellular memory mechanism that maintains gene expression states established by other regulators. In general, PcG proteins are responsible for maintaining a repressed expression state, whereas trxG proteins act in opposition to maintain an active expression state. This mechanism, first discovered in Drosophila and subsequently in mammals, has more recently been studied in plants. The characterization of several Polycomb Repressive Complex 2 (PRC2) components in Arabidopsis thaliana constituted a first breakthrough, revealing key roles of PcG proteins in the control of crucial plant developmental processes. Interestingly, the recent identification of plant homologues of the Drosophila trithorax protein suggests a conservation of both the PcG and trxG gene regulatory system in plants. Here, we review the current evidence for the role of PcG and trxG proteins in the control of plant development, their biochemical functions, their interplay in maintaining stable expression states of their target genes, and point out future directions which may help our understanding of PcG and trxG function in plants.