scholarly journals The controversial role of the Polycomb group proteins in transcription and cancer: how much do we not understand Polycomb proteins?

FEBS Journal ◽  
2014 ◽  
Vol 282 (9) ◽  
pp. 1703-1722 ◽  
Author(s):  
Andrea Scelfo ◽  
Andrea Piunti ◽  
Diego Pasini
Keyword(s):  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Polycomb Proteins

Polycomb proteins in hematologic malignancies

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5465-5475 ◽  
Author(s):  
Daniel Martin-Perez ◽  
Miguel A. Piris ◽  
Margarita Sanchez-Beato
Keyword(s):  
Stem Cell ◽  
Cell Function ◽  
Chromatin Modification ◽  
Hematologic Malignancies ◽  
Polycomb Group ◽  
Major Mechanism ◽  
Polycomb Proteins ◽  
Frequent Event ◽  
Health And Disease

Abstract The Polycomb group (PcG) of proteins is a major mechanism of epigenetic regulation that has been broadly linked to cancer. This system can repress gene expression by chromatin modification and is essential for establishing cell identity. PcG proteins are important for stem cell function and differentiation and have a profound impact during hematopoiesis. In recent years, several published studies have deepened our knowledge of the biology of the PcG in health and disease. In this article, we review the current understanding of the mechanisms of PcG-mediated repression and their relation to DNA methylation, and we discuss the role of the PcG system in hematopoiesis and hematologic malignancies. We suggest that alteration of different PcG members is a frequent event in leukemia and lymphomas that confers the stem cell properties on tumor cells. Thus, drugs targeting Polycomb complexes could be useful for treating patients with these diseases.

The role of polycomb group proteins and KDM2B in leukemia

2016 ◽  
Vol 44 (9) ◽  
pp. S104-S105
Author(s):  
Vincent van den Boom ◽  
Bauke de Boer ◽  
Maia Elliott ◽  
Pierre-Olivier Angrand ◽  
Edo Vellenga ◽  
...  
Keyword(s):  
Polycomb Group ◽  
Polycomb Group Proteins

scholarly journals The role of Polycomb Group Proteins in Cell Cycle Regulation During Development

Cell Cycle ◽  
2006 ◽  
Vol 5 (11) ◽  
pp. 1189-1197 ◽  
Author(s):  
Anne-Marie Martinez ◽  
Giacomo Cavalli
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Cycle Regulation

scholarly journals Role of Polycomb group proteins in the hepatic stem cell self-renewal

2009 ◽  
Vol 53 (4) ◽  
pp. 115-119
Author(s):  
Yasuharu Ueno ◽  
Takako Naito ◽  
Hideki Taniguchi
Keyword(s):  
Stem Cell ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Self Renewal ◽  
Hepatic Stem Cell

Role of Polycomb Group Proteins in Stem Cell Self-Renewal and Cancer

2005 ◽  
Vol 24 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Jesús Gil ◽  
David Bernard ◽  
Gordon Peters
Keyword(s):  
Stem Cell ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Self Renewal

scholarly journals Transcription-replication conflicts as a source of common fragile site instability caused by BMI1-RNF2 deficiency

2019 ◽  
Author(s):  
Anthony Sanchez ◽  
Angelo de Vivo ◽  
Peter Tonzi ◽  
Jeonghyeon Kim ◽  
Tony T. Huang ◽  
...  
Keyword(s):  
Protective Factor ◽  
Fragile Site ◽  
Fragile Sites ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Genome Maintenance ◽  
Cancer Etiology ◽  
Genomic Aberration ◽  
Common Fragile Sites ◽  
Polycomb Proteins

AbstractCommon fragile sites (CFSs) are breakage-prone genomic loci, and are considered to be hotspots for genomic rearrangements frequently observed in cancers. Understanding the underlying mechanisms for CFS instability will lead to better insight on cancer etiology. Here we show that Polycomb group proteins BMI1 and RNF2 are suppressors of transcription-replication conflicts (TRCs) and CFS instability. Cells depleted of BMI1 or RNF2 showed slower replication forks and elevated fork stalling. These phenotypes are associated with increase occupancy of RNA Pol II (RNAPII) at CFSs, suggesting that the BMI1-RNF2 complex regulate RNAPII elongation at these fragile regions. Using proximity ligase assays, we showed that depleting BMI1 or RNF2 causes increased associations between RNAPII with EdU-labeled nascent forks and replisomes, suggesting increased TRC incidences. Increased occupancy of a fork protective factor FANCD2 and R-loop resolvase RNH1 at CFSs are observed in RNF2 CRISPR-KO cells, which are consistent with increased transcription-associated replication stress in RNF2-deficient cells. Depleting FANCD2 or FANCI proteins further increased genomic instability and cell death of the RNF2-deficient cells, suggesting that in the absence of RNF2, cells depend on these fork-protective factors for survival. These data suggest that the Polycomb proteins have non-canonical roles in suppressing TRC and preserving genomic integrity.Author summaryIncreasing evidence suggest that instabilities at common fragile sites (CFSs), breakage-prone genomic loci, may be source of genomic aberration seen in cancer cells. Among the proposed mechanisms that can cause CFSs instabilities is the conflict between transcription and replication, and the mechanisms or factors that resolve the possible conflicts are only beginning to be understood. Here we found that deficiency in the Polycomb group proteins BMI1 or RNF2 leads to the CFS instability, and is associated with transcription-associated replication fork stresses. We further found that in the absence of RNF2, cells depend on the Fanconi Anemia fork-protective proteins for genome maintenance and survival. These results underscore that the Polycomb proteins are important for genome maintenance.

Polycomb Group Repression Is Blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] Insulator

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 331-339
Author(s):  
Daniel R Mallin ◽  
Jane S Myung ◽  
J Scott Patton ◽  
Pamela K Geyer
Keyword(s):  
Reporter Genes ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Binding Region ◽  
Position Effects ◽  
Response Element ◽  
Polycomb Group Genes ◽  
Chromosomal Position ◽  
Group Response

Abstract The suppressor of Hairy-wing [SU(HW)] binding region disrupts communication between a large number of enhancers and promoters and protects transgenes from chromosomal position effects. These properties classify the SU(HW) binding region as an insulator. While enhancers are blocked in a general manner, protection from repressors appears to be more variable. In these studies, we address whether repression resulting from the Polycomb group genes can be blocked by the SU(HW) binding region. The effects of this binding region on repression established by an Ultrabithorax Polycomb group Response Element were examined. A transposon carrying two reporter genes, the yellow and white genes, was used so that repression and insulation could be assayed simultaneously. We demonstrate that the SU(HW) binding region is effective at preventing Polycomb group repression. These studies suggest that one role of the su(Hw) protein may be to restrict the range of action of repressors, such as the Polycomb group proteins, throughout the euchromatic regions of the genome.

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