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.

scholarly journals SUMOylation of the polycomb group protein L3MBTL2 facilitates repression of its target genes

2013 ◽  
Vol 42 (5) ◽  
pp. 3044-3058 ◽  
Author(s):  
Christina Stielow ◽  
Bastian Stielow ◽  
Florian Finkernagel ◽  
Maren Scharfe ◽  
Michael Jarek ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Target Genes ◽  
Polycomb Group ◽  
Hek293 Cells ◽  
Polycomb Group Protein ◽  
Wild Type ◽  
C Terminus ◽  
Lysine Residues ◽  
Group Protein

Abstract Lethal(3) malignant brain tumour like 2 (L3MBTL2) is an integral component of the polycomb repressive complex 1.6 (PRC1.6) and has been implicated in transcriptional repression and chromatin compaction. Here, we show that L3MBTL2 is modified by SUMO2/3 at lysine residues 675 and 700 close to the C-terminus. SUMOylation of L3MBTL2 neither affected its repressive activity in reporter gene assays nor it’s binding to histone tails in vitro. In order to analyse whether SUMOylation affects binding of L3MBTL2 to chromatin, we performed ChIP-Seq analysis with chromatin of wild-type HEK293 cells and with chromatin of HEK293 cells stably expressing either FLAG-tagged SUMOylation-competent or SUMOylation-defective L3MBTL2. Wild-type FLAG-L3MBTL2 and the SUMOylation-defective FLAG-L3MBTL2 K675/700R mutant essentially occupied the same sites as endogenous L3MBTL2 suggesting that SUMOylation of L3MBTL2 does not affect chromatin binding. However, a subset of L3MBTL2-target genes, particularly those with low L3MBTL2 occupancy including pro-inflammatory genes, was de-repressed in cells expressing the FLAG-L3MBTL2 K675/700R mutant. Finally, we provide evidence that SUMOylation of L3MBTL2 facilitates repression of these PRC1.6-target genes by balancing the local H2Aub1 levels established by the ubiquitinating enzyme RING2 and the de-ubiquitinating PR–DUB complex.

scholarly journals The Polycomb group protein MEDEA controls cell proliferation and embryonic patterning in Arabidopsis

2021 ◽  
Author(s):  
Sara Simonini ◽  
Marian Bemer ◽  
Stefano Bencivenga ◽  
Valeria Gagliardini ◽  
Nuno D. Pires ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Polycomb Group ◽  
Embryonic Patterning ◽  
Polycomb Group Protein ◽  
Group Protein

scholarly journals The Polycomb group protein MEDEA controls cell proliferation and embryonic patterning in Arabidopsis

2020 ◽  
Author(s):  
Sara Simonini ◽  
Marian Bemer ◽  
Stefano Bencivenga ◽  
Valeria Gagliardini ◽  
Nuno D. Pires ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lineage ◽  
Embryonic Cell ◽  
The Body ◽  
Polycomb Group ◽  
Normal Embryo ◽  
Embryonic Patterning ◽  
Polycomb Group Protein ◽  
Group Protein

Establishing the body plan of a multicellular organism relies on precisely orchestrated cell divisions coupled with pattern formation. In animals, cell proliferation and embryonic patterning are regulated by Polycomb group (PcG) proteins that form various multisubunit complexes (Grossniklaus and Paro, 2014). The evolutionary conserved Polycomb Repressive Complex 2 (PRC2) trimethylates histone H3 at lysine 27 (H3K27me3) and comes in different flavors in the model plant Arabidopsis thaliana (Förderer et al., 2016; Grossniklaus and Paro, 2014). The histone methyltransferase MEDEA (MEA) is part of the FERTILIZATION INDEPENDENT SEED (FIS)-PRC2 required for seed development4. Although embryos derived from mea mutant egg cells show morphological abnormalities (Grossniklaus et al., 1998), defects in the development of the placenta-like endosperm are considered the main cause of seed abortion (Kinoshita et al., 1999; Scott et al., 1998), and a role of FIS-PRC2 in embryonic patterning was dismissed (Bouyer et al., 2011; Leroy et al., 2007). Here, we demonstrate that endosperm lacking MEA activity sustains normal embryo development and that embryos derived from mea mutant eggs abort even in presence of a wild-type endosperm because MEA is required for embryonic patterning and cell lineage determination. We show that, similar to PcG proteins in mammals, MEA regulates embryonic growth by repressing the transcription of core cell cycle components. Our work demonstrates that Arabidopsis embryogenesis is under epigenetic control of maternally expressed PcG proteins, revealing that PRC2 was independently recruited to control embryonic cell proliferation and patterning in animals and plants.

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 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 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 Retinoic Acid Receptor Isotype Specificity in F9 Teratocarcinoma Stem Cells Results from the Differential Recruitment of Coregulators to Retinoic Acid Response Elements

2007 ◽  
Vol 282 (46) ◽  
pp. 33421-33434 ◽  
Author(s):  
Robert F. Gillespie ◽  
Lorraine J. Gudas
Keyword(s):  
Stem Cells ◽  
Retinoic Acid ◽  
Target Genes ◽  
Retinoic Acid Receptor ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Response Elements ◽  
Acid Receptor ◽  
Group Protein ◽  
F9 Teratocarcinoma

The retinoic acid receptor (RAR) α, β2, and γ isotypes each regulate specific subsets of target genes in F9 teratocarcinoma stem cells. We used chromatin immunoprecipitation assays to monitor the association of RARγ, retinoic X receptor (RXR) α, and coregulators with the RARβ2, Hoxa1, and Cyp26A1 retinoic acid response elements (RAREs) in F9 wild type and RARα, -β2, and -γ null cells. Additionally we quantitatively monitored expression of the corresponding mRNAs. We demonstrated that the association of RARγ and/or RXRα with a RARE was not sufficient for retinoic acid (RA)-mediated transcription of the corresponding target gene. However, the ability of RARγ and/or RXRα to recruit pCIP (AIB1/ACTR/RAC-3/TRAM-1/SRC-3) and p300 to a RARE did correlate with RA-associated transcription of target mRNAs. Therefore, the specific functions of the RAR isotypes do not manifest at the level of their DNA binding but rather from a differential ability to recruit specific components of the transcriptional machinery. We also demonstrated that RA-mediated displacement of the polycomb group protein SUZ12 from a RARE was inhibited in the absence of RARγ. Thus, transcriptional components of the RAR signaling pathway are specifically required for displacement of SUZ12 from RAREs during RA-mediated differentiation of F9 cells.

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