scholarly journals Interactions with RNA direct the Polycomb group protein SCML2 to chromatin where it represses target genes

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Roberto Bonasio ◽  
Emilio Lecona ◽  
Varun Narendra ◽  
Philipp Voigt ◽  
Fabio Parisi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epigenetic Regulation ◽  
Target Genes ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Binding Region ◽  
Group Protein ◽  
Polycomb Repressive Complex 1

Polycomb repressive complex-1 (PRC1) is essential for the epigenetic regulation of gene expression. SCML2 is a mammalian homolog of Drosophila SCM, a Polycomb-group protein that associates with PRC1. In this study, we show that SCML2A, an SCML2 isoform tightly associated to chromatin, contributes to PRC1 localization and also directly enforces repression of certain Polycomb target genes. SCML2A binds to PRC1 via its SPM domain and interacts with ncRNAs through a novel RNA-binding region (RBR). Targeting of SCML2A to chromatin involves the coordinated action of the MBT domains, RNA binding, and interaction with PRC1 through the SPM domain. Deletion of the RBR reduces the occupancy of SCML2A at target genes and overexpression of a mutant SCML2A lacking the RBR causes defects in PRC1 recruitment. These observations point to a role for ncRNAs in regulating SCML2 function and suggest that SCML2 participates in the epigenetic control of transcription directly and in cooperation with PRC1.

scholarly journals USP7 Cooperates with SCML2 To Regulate the Activity of PRC1

2015 ◽  
Vol 35 (7) ◽  
pp. 1157-1168 ◽  
Author(s):  
Emilio Lecona ◽  
Varun Narendra ◽  
Danny Reinberg
Keyword(s):  
Chromatin Immunoprecipitation ◽  
Essential Role ◽  
Target Genes ◽  
Polycomb Group ◽  
Histone H2a ◽  
Polycomb Group Protein ◽  
Specific Component ◽  
Group Protein ◽  
The Common ◽  
Polycomb Repressive Complex 1

USP7 is a protein deubiquitinase with an essential role in development. Here, we provide evidence that USP7 regulates the activity of Polycomb repressive complex 1 (PRC1) in coordination with SCML2. There are six versions of PRC1 defined by the association of one of the PCGF homologues (PCGF1 to PCGF6) with the common catalytic subunit RING1B. First, we show that SCML2, a Polycomb group protein that associates with PRC1.2 (containing PCGF2/MEL18) and PRC1.4 (containing PCGF4/BMI1), modulates the localization of USP7 and bridges USP7 with PRC1.4, allowing for the stabilization of BMI1. Chromatin immunoprecipitation (ChIP) experiments demonstrate that USP7 is found at SCML2 and BMI1 target genes. Second, inhibition of USP7 leads to a reduction in the level of ubiquitinated histone H2A (H2Aub), the catalytic product of PRC1 and key for its repressive activity. USP7 regulates the posttranslational status of RING1B and BMI1, a specific component of PRC1.4. Thus, not only does USP7 stabilize PRC1 components, its catalytic activity is also necessary to maintain a functional PRC1, thereby ensuring appropriate levels of repressive H2Aub.

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

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2457-2467 ◽  
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.

scholarly journals The primary microRNA-208b interacts with Polycomb-group protein, Ezh2, to regulate gene expression in the heart

2013 ◽  
Vol 42 (2) ◽  
pp. 790-803 ◽  
Author(s):  
P. Mathiyalagan ◽  
J. Okabe ◽  
L. Chang ◽  
Y. Su ◽  
X.-J. Du ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Regulate Gene Expression ◽  
Group Protein ◽  
Regulate Gene

scholarly journals SIRT1 affects DNA methylation of polycomb group protein target genes, a hotspot of the epigenetic shift observed in ageing

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Luisa A Wakeling ◽  
Laura J Ions ◽  
Suzanne M Escolme ◽  
Simon J Cockell ◽  
Tianhong Su ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Target Genes ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Protein Target ◽  
Group Protein

scholarly journals Cbx2, a Polycomb Group Gene, Is Required for Sry Gene Expression in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 913-924 ◽  
Author(s):  
Yuko Katoh-Fukui ◽  
Kanako Miyabayashi ◽  
Tomoko Komatsu ◽  
Akiko Owaki ◽  
Takashi Baba ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gonadal Development ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Rt Pcr ◽  
Sry Gene ◽  
Genes Encoding ◽  
Group Protein ◽  
Male To Female ◽  
Immunohistochemical Analyses

Mice lacking the function of the polycomb group protein CBX2 (chromobox homolog 2; also known as M33) show defects in gonadal, adrenal, and splenic development. In particular, XY knockout (KO) mice develop ovaries but not testes, and the gonads are hypoplastic in both sexes. However, how CBX2 regulates development of these tissues remains largely unknown. In the present study, we used microarray, RT-PCR, and immunohistochemical analyses to show that the expression of Sry, Sox9, Lhx9, Ad4BP/SF-1, Dax-1, Gata4, Arx, and Dmrt1, genes encoding transcription factors essential for gonadal development, is affected in Cbx2 KO gonads. Male-to-female sex reversal in Cbx2 KO mice was rescued by crossing them with transgenic mice displaying forced expression of Sry or Sox9. However, testes remained hypoplastic in these mice, indicating that the size and the sex of the gonad are determined by different sets of genes. Our study implicates Cbx2 in testis differentiation through regulating Sry gene expression.

scholarly journals Polycomb Group Protein Suppressor 2 of Zeste Is a Functional Homolog of Posterior Sex Combs

2008 ◽  
Vol 29 (2) ◽  
pp. 515-525 ◽  
Author(s):  
Stanley M. Lo ◽  
Nitin K. Ahuja ◽  
Nicole J. Francis
Keyword(s):  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Small Region ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Functional Homolog ◽  
Sex Combs ◽  
Functional Complex ◽  
Group Protein ◽  
Polycomb Repressive Complex 1

ABSTRACT The Drosophila melanogaster Polycomb group protein Posterior Sex Combs is a component of Polycomb repressive complex 1 and is central to Polycomb group-mediated silencing. A related Polycomb group gene, Suppressor 2 of zeste, is thought to be partially redundant in function. The two proteins share a small region of homology but also contain regions of unconserved sequences. Here we report a biochemical characterization of Suppressor 2 of zeste. Like Posterior Sex Combs, Suppressor 2 of zeste binds DNA, compacts chromatin, and inhibits chromatin remodeling. Interestingly, the regions of the two proteins responsible for these activities lack sequence homology. Suppressor 2 of zeste can also replace Posterior Sex Combs in a functional complex with other Polycomb group proteins, but unlike with their biochemical activities, complex formation is mediated by the region of Suppressor 2 of zeste that is homologous to that of Posterior Sex Combs. Our results establish Suppressor 2 of zeste as a functional homolog of Posterior Sex Combs and suggest that the two proteins operate via similar molecular mechanisms.

scholarly journals Characterization of Interactions between the Mammalian Polycomb-Group Proteins Enx1/EZH2 and EED Suggests the Existence of Different Mammalian Polycomb-Group Protein Complexes

1998 ◽  
Vol 18 (6) ◽  
pp. 3586-3595 ◽  
Author(s):  
Richard G. A. B. Sewalt ◽  
Johan van der Vlag ◽  
Marco J. Gunster ◽  
Karien M. Hamer ◽  
Jan L. den Blaauwen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Complexes ◽  
Expression Patterns ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Sex Combs ◽  
Group Protein ◽  
Nuclear Domains ◽  
Z Protein

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.

Sign in / Sign up

Export Citation Format

Share Document