Involvement of the Polycomb-group geneRing1Bin the specification of the anterior-posterior axis in mice

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4171-4183 ◽  
Author(s):  
Maki Suzuki ◽  
Yoko Mizutani-Koseki ◽  
Yu-ichi Fujimura ◽  
Hiro Miyagishima ◽  
Tomomi Kaneko ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Hox Genes ◽  
Protein Complexes ◽  
Mouse Genome Informatics ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Chromosomal Dna ◽  
Polycomb Group Genes ◽  
Group Protein

The products of the Polycomb group of genes form complexes that maintain the state of transcriptional repression of several genes with relevance to development and in cell proliferation. We have identified Ring1B, the product of the Ring1B gene (Rnf2 – Mouse Genome Informatics), by means of its interaction with the Polycomb group protein Mel18. We describe biochemical and genetic studies directed to understand the biological role of Ring1B. Immunoprecipitation studies indicate that Ring1B form part of protein complexes containing the products of other Polycomb group genes, such as Rae28/Mph1 and M33, and that this complexes associate to chromosomal DNA. We have generated a mouse line bearing a hypomorphic Ring1B allele, which shows posterior homeotic transformations of the axial skeleton and a mild derepression of some Hox genes (Hoxb4, Hoxb6 and Hoxb8) in cells anterior to their normal boundaries of expression in the mesodermal compartment. By contrast, the overexpression of Ring1B in chick embryos results in the repression of Hoxb9 expression in the neural tube. These results, together with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are consistent with a role for Ring1B in the regulation of Hox gene expression by Polycomb group complexes.

Genetic interactions and dosage effects of Polycomb group genes in mice

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3543-3551 ◽  
Author(s):  
S. Bel ◽  
N. Core ◽  
M. Djabali ◽  
K. Kieboom ◽  
N. Van der Lugt ◽  
...  
Keyword(s):  
Hox Genes ◽  
Expression Patterns ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Genetic Interactions ◽  
Homeotic Gene ◽  
Polycomb Group Genes ◽  
Dosage Effects ◽  
Somitic Mesoderm ◽  
Homeotic Gene Expression

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes. These skeletal transformations are accompanied with an enhanced shift of the anterior limit of expression of several Hox genes in the somitic mesoderm. Our results demonstrate that in mice the Polycomb group genes act in synergy to control the nested expression pattern of some Hox genes in somitic mesodermal tissues during development.

scholarly journals A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
Author(s):  
Anna L. F. V. Assumpção ◽  
Guoping Fu ◽  
Deependra K. Singh ◽  
Zhanping Lu ◽  
Ashley M. Kuehnl ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Function ◽  
Transcriptional Repression ◽  
T Cell Development ◽  
Cell Development ◽  
Polycomb Group ◽  
Conditional Knockout ◽  
Specific Requirement ◽  
Polycomb Group Protein ◽  
Group Protein

ABSTRACT Yin Yang 1 (YY1) is a ubiquitous transcription factor and mammalian Polycomb Group protein (PcG) with important functions for regulating lymphocyte development and stem cell self-renewal. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that result in histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in the hematopoietic system results in an early T cell developmental blockage at the double negative (DN) 1 stage with reduced Notch1 signaling. There is a lineage-specific requirement for YY1 PcG function. YY1 PcG domain is required for T and B cell development but not necessary for myeloid cells. YY1 functions in early T cell development are multicomponent and involve both PcG-dependent and -independent regulations. Although YY1 promotes early T cell survival through its PcG function, its function to promote the DN1-to-DN2 transition and Notch1 expression and signaling is independent of its PcG function. Our results reveal how a ubiquitously expressed PcG protein mediates lineage-specific and context-specific functions to control early T cell development.

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.

Altered cellular proliferation and mesoderm patterning in Polycomb-M33-deficient mice

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 721-729 ◽  
Author(s):  
N. Core ◽  
S. Bel ◽  
S.J. Gaunt ◽  
M. Aurrand-Lions ◽  
J. Pearce ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Hox Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Polycomb Group Genes

In Drosophila, the trithorax-group and the Polycomb-group genes are necessary to maintain the expression of the homeobox genes in the appropriate segments. Loss-of-function mutations in those groups of genes lead to misexpression of the homeotic genes resulting in segmental homeotic transformations. Recently, mouse homologues of the Polycomb-group genes were identified including M33, the murine counterpart of Polycomb. In this report, M33 was targeted in mice by homologous recombination in embryonic stem (ES) cells to assess its function during development. Homozygous M33 (−/−) mice show greatly retarded growth, homeotic transformations of the axial skeleton, sternal and limb malformations and a failure to expand in vitro of several cell types including lymphocytes and fibroblasts. In addition, M33 null mutant mice show an aggravation of the skeletal malformations when treated to RA at embryonic day 7.5, leading to the hypothesis that, during development, the M33 gene might play a role in defining access to retinoic acid response elements localised in the regulatory regions of several Hox genes.

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

Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2469-2478 ◽  
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.

scholarly journals Mel-18, a Polycomb Group Protein, Regulates Cell Proliferation and Senescence via Transcriptional Repression of Bmi-1 and c-Myc Oncoproteins

2007 ◽  
Vol 18 (2) ◽  
pp. 536-546 ◽  
Author(s):  
Wei-Jian Guo ◽  
Sonal Datta ◽  
Vimla Band ◽  
Goberdhan P. Dimri
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Human Fibroblasts ◽  
Ring Finger ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Down Regulation ◽  
Group Protein ◽  
Bona Fide

Polycomb group (PcG) protein Bmi-1 is an important regulator of cell proliferation. It regulates cellular senescence and proliferation of cells via the transcriptional repression of INK4a/ARF locus and other target genes. Here, we report that Mel-18, a PcG ring finger protein (PCGF) transcriptionally down-regulates Bmi-1. Furthermore, the expression of Bmi-1 and Mel-18 inversely correlates in proliferating and senescent human fibroblasts. Bmi-1 down-regulation by Mel-18 results in accelerated senescence and shortening of the replicative life span in normal human cells. Importantly, using promoter-reporter, chromatin immunoprecipitation, and quantitative real-time primary transcript RT-PCR assays, and an RNA interference approach, we demonstrate that Bmi-1 is a bona fide target of c-Myc oncoprotein. Finally, our data suggest that Mel-18 regulates Bmi-1 expression during senescence via down-regulation of c-Myc. These studies link c-Myc and polycomb function in cell proliferation and senescence.

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