Trends in Cell Biology
ReviewProgramming of gene expression by Polycomb group proteins
Introduction
Polycomb group (PcG) proteins were first discovered in the fruit fly Drosophila melanogaster. In Drosophila as well as in other organisms, the family of PcG proteins are required for the control of body segmentation by preventing inappropriate expression of homeotic (Hox) genes. Later work demonstrated that PcG proteins are master regulators of so-called genomic programs – owing to their ability to maintain genes in an active or repressed state, dependent on the differentiation status over many cell divisions [1]. It appears that, in any particular cell type, PcG proteins repress all alternative genetic programs that are not needed. Consequently, PcG proteins are required to maintain stem cell identity, and they do this by suppressing key regulators of differentiation pathways 2, 3, 4. In this review, we discuss recent progress in our understanding of PcG function by highlighting similarities and differences of PcG action in Drosophila, mammals and plants. Several aspects of PcG proteins will not be discussed in our review, because they have recently been covered by other reviews. These aspects include the role of PcG proteins in mammalian X chromosome inactivation [5] and in genomic imprinting 6, 7.
Section snippets
PcG complexes
PcG proteins assemble as high molecular weight complexes. They were initially purified from Drosophila, but homologous complexes were later isolated in other organisms (Table 1). Drosophila has three different PcG complexes – Polycomb repressive complex 1 (PRC1), Polycomb repressive complex 2 (PRC2) and Pleiohomeotic repressive complex (PhoRC). PRC2 is thought to be involved in the initiation of gene silencing, whereas PRC1 is implicated in the stable maintenance of gene repression [8]. The
Biological functions of PcG proteins
Although it was long suspected that PcG proteins regulate not only Hox genes but many more targets, only the recently applied combination of chromatin immunoprecipitation (ChIP) with microarray analysis (ChIP-on-Chip) revealed that PcG proteins are involved in all the main developmental pathways in flies and mammals [1]. They are likely to repress alternative genetic programs that are not needed in any particular cell type, and they are required to maintain stem cell identity by suppressing key
Recruitment of PcG proteins to their targets
To date, the question of how PcG proteins are targeted to chromatin is still unanswered, because neither PRC1 nor PRC2 core complexes contain sequence-specific DNA binding factors. The Drosophila Pho protein is the only PcG protein with DNA binding specificity and is able to recruit PRC2 in addition to PRC1 to target loci 24, 25. However, biochemically purified Pho complexes did not contain PRC1 or PRC2 subunits, and Pho wasn’t identified as a subunit of purified PRC1 or PRC2 15, 26, suggesting
Mechanisms of H3K27me3 deposition
The biochemical composition of PRC2 complexes is conserved between Drosophila and mammals, but the mechanisms of H3K27me3 deposition differ. In Drosophila, PRC2 components were found only at restricted chromosomal regions, whereas H3K27me3 covers large domains 31, 32. By contrast, mammalian PRC2 components were found throughout the entire regions covered by H3K27me3 3, 4. In plants, H3K27me3 regions span significant proportions of their target genes, with a significant bias towards the promoter
Silencing mechanisms of PcG proteins
Although our understanding of PcG function has greatly increased during recent years, the principal mechanism of how PcG proteins achieve transcriptional repression is still unknown. The Drosophila PRC1 core complex was shown to cause compaction of nucleosomes in vitro [35], but it is not clear whether these findings reflect the in vivo situation, because there is no strong evidence for chromatin compaction by PcG proteins in vivo. Also, the connection between PRC1-mediated mono-ubiquitination
Diversification of PRC1 function
Although the PRC1 subunit Pc contains a chromodomain that binds specifically to H3K27me3 50, 51, ChIP experiments revealed no close overlap between Pc localization and H3K27me3. The H3K27me3 distribution is significantly more extended than the localization of Pc, which is mainly restricted to PREs 31, 52. This suggests that PRC1 recruitment occurs by a still undefined mechanism. Quite unexpectedly, it was recently shown that the Arabidopsis chromodomain protein LIKE HETERCHROMATIN PROTEIN1
The role of trithorax group proteins in preventing PcG-mediated repression
Genetic analysis of trx mutants suggested that trxG proteins work antagonistically to PcG proteins, a hypothesis that was subsequently supported by the finding that PcG target genes are positively regulated by trxG proteins [11]. Similar observations were recently also made in plants. Mutants of the PcG gene CLF ectopically express the floral organ identity gene AG, form curled leaves and flower early [61]. By contrast, mutants of the Trx homolog ATX1 (ARABIDOPSIS TRITHORAX1) have reduced AG
Conclusions
Technologies to profile PcG proteins and histone modifications have dramatically changed our view on the action of PcG proteins during development. To obtain a comprehensive picture about the dynamics of PcG recruitment during development, chromatin and expression profiles of different developmental stages and organs need to be established and compared as a next step. Although profiling is of crucial importance, it will not on its own enable us to solve one of the most fundamental questions
Acknowledgements
We thank L. Hennig for helpful comments on the manuscript. This research was supported by the Swiss National Science Foundation (PP00A-106684/1) and ETH (TH-12 06–1) to C.K., who is also supported by a European Molecular Biology Organization (EMBO) Young Investigator Award.
References (74)
Control of developmental regulators by Polycomb in human embryonic stem cells
Cell
(2006)- et al.
Convergent evolution of genomic imprinting in plants and mammals
Trends Genet.
(2007) - et al.
Polycomb complexes and silencing mechanisms
Curr. Opin. Cell Biol.
(2004) Polycomb Group proteins: an evolutionary perspective
Trends Genet.
(2007)- et al.
Polycomb group and trithorax group proteins in Arabidopsis
Biochim. Biophys. Acta
(2007) Human SFMBT is a transcriptional repressor protein that selectively binds the N-terminal tail of histone H3
FEBS Lett.
(2007)Genome regulation by Polycomb and trithorax proteins
Cell
(2007)Hierarchical recruitment of Polycomb group silencing complexes
Mol. Cell
(2004)Histone methyltransferase activity of a Drosophila Polycomb group repressor complex
Cell
(2002)- et al.
Polycomb response elements and targeting of Polycomb group proteins in Drosophila
Curr. Opin. Genet. Dev.
(2006)
The origins of multicellularity: a multi-taxon genome initiative
Trends Genet.
Architecture of a Polycomb nucleoprotein complex
Mol. Cell
Polycomb silencing blocks transcription initiation
Mol. Cell
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
Cell
Pairing-sensitive silencing, Polycomb group response elements, and transposon homing in Drosophila
Adv. Genet.
RNAi components are required for nuclear clustering of Polycomb group response elements
Cell
Polycomb complexes and the propagation of the methylation mark at the Drosophila Ubx gene
J. Biol. Chem.
ATX-1, an Arabidopsis homolog of trithorax, activates flower homeotic genes
Curr. Biol.
The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation
Mol. Cell
Mechanisms of epigenetic inheritance
Curr. Opin. Cell Biol.
The key to development: interpreting the histone code? Curr
Opin. Genet. Dev.
Epigenetic inheritance of expression states in plant development: the role of Polycomb group proteins
Curr. Opin. Cell Biol.
MSI1-like proteins: an escort service for chromatin assembly and remodeling complexes
Trends Cell Biol.
Polycomb silencing mechanisms and the management of genomic programmes
Nat. Rev. Genet.
Polycomb complexes repress developmental regulators in murine embryonic stem cells
Nature
Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions
Genes Dev.
Dosage compensation in mammals: fine-tuning the expression of the X chromosome
Genes Dev.
Epigenetic mechanisms governing seed development in plants
EMBO Rep.
A Drosophila Polycomb group complex includes Zeste and dTAFII proteins
Nature
General transcription factors bind promoters repressed by Polycomb group proteins
Nature
The core of the Polycomb repressive complex is compositionally and functionally conserved in flies and humans
Mol. Cell. Biol.
Pcl-PRC2 is needed to generate high levels of H3-K27 trimethylation at Polycomb target genes
EMBO J.
A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysine-binding activities
Genes Dev.
Transcription factor YY1 functions as a PcG protein in vivo
EMBO J.
The Polycomb-group gene EZH2 is required for early mouse development
Mol. Cell. Biol.
Interaction of Polycomb-group proteins controlling flowering in Arabidopsis
Development
Whole-genome analysis of histone h3 lysine 27 trimethylation in Arabidopsis
PLoS Biol.
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2018, Advances in Botanical ResearchCitation Excerpt :The DNA glycosylase (or demethylase) enzymes remove 5-methylcytosine from its targets through a base excision repair mechanism and replace it with an unmethylated cytosine (Gehring et al., 2006; Morales-Ruiz et al., 2006). In Arabidopsis, AtDME was originally characterized as an epigenetic regulator required for maternal allelelic expression of the MEDEA (MEA) gene, encoding a repressive H3K27 methyltransferase, in the central cell of the embryo and endosperm (Choi et al., 2002; Kohler & Villar, 2008). Proper embryo and endosperm development depends on the expression of the maternal allele and silencing of the paternal allele (imprinting) of certain components of the Polycomb group Repressive complex2 (PRC2).