SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2

ABSTRACT In Drosophila melanogaster, thePolycomb-group (PcG) andtrithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxGgene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog ofeed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs(esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.

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The iab-7 Polycomb Response Element Maps to a Nucleosome-Free Region of Chromatin and Requires Both GAGA and Pleiohomeotic for Silencing Activity

Molecular and Cellular Biology ◽

10.1128/mcb.21.4.1311-1318.2001 ◽

2001 ◽

Vol 21 (4) ◽

pp. 1311-1318 ◽

Cited By ~ 109

Author(s):

Rakesh K. Mishra ◽

Jozsef Mihaly ◽

Stéphane Barges ◽

Annick Spierer ◽

François Karch ◽

...

Keyword(s):

Binding Sites ◽

Polycomb Group ◽

Polycomb Group Protein ◽

Gaga Factor ◽

Response Element ◽

Polycomb Response Element ◽

Free Region ◽

Group Protein

ABSTRACT In the work reported here we have undertaken a functional dissection of a Polycomb response element (PRE) from the iab-7 cis-regulatory domain of the Drosophila melanogasterbithorax complex (BX-C). Previous studies mapped the iab-7PRE to an 860-bp fragment located just distal to the Fab-7boundary. Located within this fragment is an ∼230-bp chromatin-specific nuclease-hypersensitive region called HS3. We have shown that HS3 is capable of functioning as a Polycomb-dependent silencer in vivo, inducing pairing-dependent silencing of amini-white reporter. The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. We show that GAGA and Pho interact with these sequences in vitro and that the consensus binding sites for the two proteins are critical for the silencing activity of theiab-7 PRE in vivo.

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The Polycomb group in Caenorhabditis elegans and maternal control of germline development

Development ◽

10.1242/dev.125.13.2469 ◽

1998 ◽

Vol 125 (13) ◽

pp. 2469-2478 ◽

Cited By ~ 7

Author(s):

I. Korf ◽

Y. Fan ◽

S. Strome

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Polycomb Group ◽

Polycomb Group Proteins ◽

Polycomb Group Protein ◽

Maternal Control ◽

Germline Development ◽

C Elegans ◽

Polycomb Group Genes ◽

Group Protein

Four Caenorhabditis elegans genes, mes-2, mes-3, mes-4 and mes-6, are essential for normal proliferation and viability of the germline. Mutations in these genes cause a maternal-effect sterile (i.e. mes) or grandchildless phenotype. We report that the mes-6 gene is in an unusual operon, the second example of this type of operon in C. elegans, and encodes the nematode homolog of Extra sex combs, a WD-40 protein in the Polycomb group in Drosophila. mes-2 encodes another Polycomb group protein (see paper by Holdeman, R., Nehrt, S. and Strome, S. (1998). Development 125, 2457–2467). Consistent with the known role of Polycomb group proteins in regulating gene expression, MES-6 is a nuclear protein. It is enriched in the germline of larvae and adults and is present in all nuclei of early embryos. Molecular epistasis results predict that the MES proteins, like Polycomb group proteins in Drosophila, function as a complex to regulate gene expression. Database searches reveal that there are considerably fewer Polycomb group genes in C. elegans than in Drosophila or vertebrates, and our studies suggest that their primary function is in controlling gene expression in the germline and ensuring the survival and proliferation of that tissue.

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MES-2, a maternal protein essential for viability of the germline in Caenorhabditis elegans, is homologous to a Drosophila Polycomb group protein

Development ◽

10.1242/dev.125.13.2457 ◽

1998 ◽

Vol 125 (13) ◽

pp. 2457-2467 ◽

Cited By ~ 7

Author(s):

R. Holdeman ◽

S. Nehrt ◽

S. Strome

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Germ Cells ◽

Target Genes ◽

Essential Feature ◽

Primordial Germ Cells ◽

Polycomb Group ◽

Polycomb Group Protein ◽

Maternal Contribution ◽

Group Protein

A unique and essential feature of germ cells is their immortality. In Caenorhabditis elegans, germline immortality requires the maternal contribution from four genes, mes-2, mes-3, mes-4 and mes-6. We report here that mes-2 encodes a protein similar to the Drosophila Polycomb group protein, Enhancer of zeste, and in the accompanying paper that mes-6 encodes another Polycomb group protein. The Polycomb group is responsible for maintaining proper patterns of expression of the homeotic and other genes in Drosophila. It is thought that Polycomb group proteins form heteromeric complexes and control gene expression by altering chromatin conformation of target genes. As predicted from its similarity to a Polycomb group protein, MES-2 localizes to nuclei. MES-2 is found in germline nuclei in larval and adult worms and in all nuclei in early embryos. By the end of embryogenesis, MES-2 is detected primarily in the two primordial germ cells. The correct distribution of MES-2 requires the wild-type functions of mes-3 and mes-6. We hypothesize that mes-2 encodes a maternal regulator of gene expression in the early germline; its function is essential for normal early development and viability of germ cells.

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The DNA-binding polycomb group protein pleiohomeotic mediates silencing of a Drosophila homeotic gene

Development ◽

10.1242/dev.126.17.3905 ◽

1999 ◽

Vol 126 (17) ◽

pp. 3905-3913 ◽

Cited By ~ 4

Author(s):

C. Fritsch ◽

J.L. Brown ◽

J.A. Kassis ◽

J. Muller

Keyword(s):

Dna Binding ◽

Binding Sites ◽

Point Mutations ◽

Polycomb Group ◽

Homeotic Gene ◽

Homeotic Genes ◽

Polycomb Group Protein ◽

Cis Acting ◽

Group Protein

Polycomb group (PcG) proteins repress homeotic genes in cells where these genes must remain inactive during development. This repression requires cis-acting silencers, also called PcG response elements. Currently, these silencers are ill-defined sequences and it is not known how PcG proteins associate with DNA. Here, we show that the Drosophila PcG protein Pleiohomeotic binds to specific sites in a silencer of the homeotic gene Ultrabithorax. In an Ultrabithorax reporter gene, point mutations in these Pleiohomeotic binding sites abolish PcG repression in vivo. Hence, DNA-bound Pleiohomeotic protein may function in the recruitment of other non-DNA-binding PcG proteins to homeotic gene silencers.

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The Drosophila Polycomb Group proteins ESC and E(Z) bind directly to each other and co-localize at multiple chromosomal sites

Development ◽

10.1242/dev.125.17.3483 ◽

1998 ◽

Vol 125 (17) ◽

pp. 3483-3496 ◽

Cited By ~ 7

Author(s):

F. Tie ◽

T. Furuyama ◽

P.J. Harte

Keyword(s):

Polycomb Group ◽

Homeotic Genes ◽

Polycomb Group Proteins ◽

Polycomb Group Protein ◽

Polycomb Group Genes ◽

Evolutionarily Conserved ◽

Group Protein ◽

Essential Prerequisite

The Polycomb Group gene esc encodes an evolutionarily conserved protein required for transcriptional silencing of the homeotic genes. Unlike other Polycomb Group genes, esc is expressed and apparently required only during early embryogenesis, suggesting it is required for the initial establishment of silencing but not for its subsequent maintenance. We present evidence that the ESC protein interacts directly with E(Z), another Polycomb Group protein required for silencing of the homeotic genes. We show that the most highly conserved region of ESC, containing seven WD motifs that are predicted to fold into a beta-propeller structure, mediate its binding to a conserved N-terminal region of E(Z). Mutations in the WD region that perturb ESC silencing function in vivo also perturb binding to E(Z) in vitro. The entire WD region forms a trypsin-resistant structure, like known beta -propeller domains, and mutations that would affect the predicted ESC beta-propeller perturb its trypsin-resistance, while a putative structure-conserving mutation does not. We show by co-immunoprecipitation that ESC and E(Z) are directly associated in vivo and that they also co-localize at many chromosomal binding sites. Since E(Z) is required for binding of other Polycomb Group proteins to chromosomes, these results suggest that formation of an E(Z):ESC complex at Polycomb Response Elements may be an essential prerequisite for the establishment of silencing.

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Biochemical mechanisms of gene regulation by polycomb group protein complexes

Current Opinion in Genetics & Development ◽

10.1016/j.gde.2009.03.001 ◽

2009 ◽

Vol 19 (2) ◽

pp. 150-158 ◽

Cited By ~ 161

Author(s):

Jürg Müller ◽

Peter Verrijzer

Keyword(s):

Gene Regulation ◽

Protein Complexes ◽

Polycomb Group ◽

Polycomb Group Protein ◽

Group Protein ◽

Biochemical Mechanisms

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SUMO modification of the Polycomb group protein Sex comb on midleg (Scm) counteracts its function as a repressor of homeotic genes

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.843.1 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Albert J Courey ◽

Matthew Smith ◽

Jeffrey A. Simon ◽

Daniel R. Mallin

Keyword(s):

Polycomb Group ◽

Homeotic Genes ◽

Polycomb Group Protein ◽

Sumo Modification ◽

Sex Comb ◽

Group Protein

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The polycomb group protein complex of Drosophila melanogaster has different compositions at different target genes.

Molecular and Cellular Biology ◽

10.1128/mcb.17.12.6773 ◽

1997 ◽

Vol 17 (12) ◽

pp. 6773-6783 ◽

Cited By ~ 87

Author(s):

H Strutt ◽

R Paro

Keyword(s):

Protein Complex ◽

Target Genes ◽

Regulatory Elements ◽

Polycomb Group ◽

Regulatory Sequences ◽

Polycomb Group Protein ◽

Polycomb Group Genes ◽

Sex Combs ◽

Group Protein

In Drosophila the Polycomb group genes are required for the long-term maintenance of the repressed state of many developmental regulatory genes. Their gene products are thought to function in a common multimeric complex that associates with Polycomb group response elements (PREs) in target genes and regulates higher-order chromatin structure. We show that the chromodomain of Polycomb is necessary for protein-protein interactions within a Polycomb-Polyhomeotic complex. In addition, Posterior Sex Combs protein coimmunoprecipitates Polycomb and Polyhomeotic, indicating that they are members of a common multimeric protein complex. Immunoprecipitation experiments using in vivo cross-linked chromatin indicate that these three Polycomb group proteins are associated with identical regulatory elements of the selector gene engrailed in tissue culture cells. Polycomb, Polyhomeotic, and Posterior Sex Combs are, however, differentially distributed on regulatory sequences of the engrailed-related gene invected. This suggests that there may be multiple different Polycomb group protein complexes which function at different target sites. Furthermore, Polyhomeotic and Posterior Sex Combs are also associated with expressed genes. Polyhomeotic and Posterior Sex Combs may participate in a more general transcriptional mechanism that causes modulated gene repression, whereas the inclusion of Polycomb protein in the complex at PREs leads to stable silencing.

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