scholarly journals Polycomb-Mediated Chromatin Loops Revealed by a Sub-Kilobase Resolution Chromatin Interaction Map

2017 ◽  
Author(s):  
Kyle P. Eagen ◽  
Erez Lieberman Aiden ◽  
Roger D. Kornberg
Keyword(s):  
Polycomb Group ◽  
Dna Looping ◽  
Gene Repression ◽  
Chromatin Interaction ◽  
Chromatin Loops ◽  
A Subunit ◽  
High Throughput Dna Sequencing ◽  
Interaction Map ◽  
Polycomb Repressive Complex 1 ◽  
Chemical Cross Linking

ABSTRACTThe locations of chromatin loops in Drosophila were determined by Hi-C (chemical cross-linking, restriction digestion, ligation, and high-throughput DNA sequencing). Whereas most loop boundaries or “anchors” are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of Polycomb Repressive Complex 1 (PRC1). Loops were frequently located within domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors. Although DNA looping has most commonly been associated with enhancer-promoter communication, our results indicate that loops are also associated with gene repression.

scholarly journals Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map

2017 ◽  
Vol 114 (33) ◽  
pp. 8764-8769 ◽  
Author(s):  
Kyle P. Eagen ◽  
Erez Lieberman Aiden ◽  
Roger D. Kornberg
Keyword(s):  
Polycomb Group ◽  
Dna Looping ◽  
Gene Repression ◽  
Chromatin Interaction ◽  
Chromatin Loops ◽  
A Subunit ◽  
High Throughput Dna Sequencing ◽  
Interaction Map ◽  
Polycomb Repressive Complex 1 ◽  
Chemical Cross Linking

The locations of chromatin loops in Drosophila were determined by Hi-C (chemical cross-linking, restriction digestion, ligation, and high-throughput DNA sequencing). Whereas most loop boundaries or “anchors” are associated with CTCF protein in mammals, loop anchors in Drosophila were found most often in association with the polycomb group (PcG) protein Polycomb (Pc), a subunit of polycomb repressive complex 1 (PRC1). Loops were frequently located within domains of PcG-repressed chromatin. Promoters located at PRC1 loop anchors regulate some of the most important developmental genes and are less likely to be expressed than those not at PRC1 loop anchors. Although DNA looping has most commonly been associated with enhancer–promoter communication, our results indicate that loops are also associated with gene repression.

scholarly journals PHC1 maintains pluripotency by organizing genome-wide chromatin interactions of the Nanog locus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Li Chen ◽  
Qiaoqiao Tong ◽  
Xiaowen Chen ◽  
Penglei Jiang ◽  
Hua Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Gene Activation ◽  
Polycomb Group ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Determination Process ◽  
A Subunit ◽  
Polycomb Repressive Complex 1 ◽  
Pluripotency Maintenance

AbstractPolycomb group (PcG) proteins maintain cell identity by repressing gene expression during development. Surprisingly, emerging studies have recently reported that a number of PcG proteins directly activate gene expression during cell fate determination process. However, the mechanisms by which they direct gene activation in pluripotency remain poorly understood. Here, we show that Phc1, a subunit of canonical polycomb repressive complex 1 (cPRC1), can exert its function in pluripotency maintenance via a PRC1-independent activation of Nanog. Ablation of Phc1 reduces the expression of Nanog and overexpression of Nanog partially rescues impaired pluripotency caused by Phc1 depletion. We find that Phc1 interacts with Nanog and activates Nanog transcription by stabilizing the genome-wide chromatin interactions of the Nanog locus. This adds to the already known canonical function of PRC1 in pluripotency maintenance via a PRC1-dependent repression of differentiation genes. Overall, our study reveals a function of Phc1 to activate Nanog transcription through regulating chromatin architecture and proposes a paradigm for PcG proteins to maintain pluripotency.

scholarly journals Asxl1 C-terminal mutation perturbs neutrophil differentiation in zebrafish

Leukemia ◽  
2021 ◽  
Author(s):  
Xiao Fang ◽  
Song’en Xu ◽  
Yiyue Zhang ◽  
Jin Xu ◽  
Zhibin Huang ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Chronic Myelomonocytic Leukemia ◽  
Nonsense Mutations ◽  
Myeloid Malignancies ◽  
A Subunit ◽  
Neutrophil Differentiation ◽  
Polycomb Repressive Complex 1 ◽  
Myelomonocytic Leukemia ◽  
Inhibitor Treatment ◽  
Acute Myeloid

AbstractASXL1 is one of the most frequently mutated genes in malignant myeloid diseases. In patients with myeloid malignancies, ASXL1 mutations are usually heterozygous frameshift or nonsense mutations leading to C-terminal truncation. Current disease models have predominantly total loss of ASXL1 or overexpressed C-terminal truncations. These models cannot fully recapitulate leukemogenesis and disease progression. We generated an endogenous C-terminal-truncated Asxl1 mutant in zebrafish that mimics human myeloid malignancies. At the embryonic stage, neutrophil differentiation was explicitly blocked. At 6 months, mutants initially exhibited a myelodysplastic syndrome-like phenotype with neutrophilic dysplasia. At 1 year, about 13% of mutants further acquired the phenotype of monocytosis, which mimics chronic myelomonocytic leukemia, or increased progenitors, which mimics acute myeloid leukemia. These features are comparable to myeloid malignancy progression in humans. Furthermore, transcriptome analysis, inhibitor treatment, and rescue assays indicated that asxl1-induced neutrophilic dysplasia was associated with reduced expression of bmi1a, a subunit of polycomb repressive complex 1 and a reported myeloid leukemia-associated gene. Our model demonstrated that neutrophilic dysplasia caused by asxl1 mutation is a foundation for the progression of myeloid malignancies, and illustrated a possible effect of the Asxl1-Bmi1a axis on regulating neutrophil development.

The domino gene of Drosophila encodes novel members of the SWI2/SNF2 family of DNA-dependent ATPases, which contribute to the silencing of homeotic genes

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1429-1441 ◽  
Author(s):  
M.L. Ruhf ◽  
A. Braun ◽  
O. Papoulas ◽  
J.W. Tamkun ◽  
N. Randsholt ◽  
...  
Keyword(s):  
Polytene Chromosomes ◽  
Gene Mutations ◽  
Polycomb Group ◽  
Protein Isoforms ◽  
Homeotic Genes ◽  
Loss Of Function ◽  
Trithorax Group ◽  
A Subunit ◽  
The Common ◽  
Hematopoietic Disorders

The Drosophila domino gene has been isolated in a screen for mutations that cause hematopoietic disorders. Generation and analysis of loss-of-function domino alleles show that the phenotypes are typical for proliferation gene mutations. Clonal analysis demonstrates that domino is necessary for cell viability and proliferation, as well as for oogenesis. domino encodes two protein isoforms of 3202 and 2498 amino acids, which contain a common N-terminal region but divergent C termini. The common region includes a 500 amino acid DNA-dependent ATPase domain of the SWI2/SNF2 family of proteins, which function via interaction with chromatin. We show that, although domino alleles do not exhibit homeotic phenotypes by themselves, domino mutations enhance Polycomb group mutations and counteract Trithorax group effects. The Domino proteins are present in large complexes in embryo extracts, and one isoform binds to a number of discrete sites on larval polytene chromosomes. Altogether, the data lead us to propose that domino acts as a repressor by interfering with chromatin structure. This activity is likely to be performed as a subunit of a chromatin-remodeling complex.

scholarly journals Identification of polycomb repressive complex 1 and 2 core components in hexaploid bread wheat

2020 ◽  
Vol 20 (S1) ◽  
Author(s):  
Beáta Strejčková ◽  
Radim Čegan ◽  
Ales Pecinka ◽  
Zbyněk Milec ◽  
Jan Šafář
Keyword(s):  
Bread Wheat ◽  
Developmental Stages ◽  
Gene Families ◽  
Polycomb Group ◽  
Transcriptional Analysis ◽  
Histone H2a ◽  
Polycomb Repressive Complex ◽  
Core Components ◽  
High Level ◽  
Polycomb Repressive Complex 1

Abstract Background Polycomb repressive complexes 1 and 2 play important roles in epigenetic gene regulation by posttranslationally modifying specific histone residues. Polycomb repressive complex 2 is responsible for the trimethylation of lysine 27 on histone H3; Polycomb repressive complex 1 catalyzes the monoubiquitination of histone H2A at lysine 119. Both complexes have been thoroughly studied in Arabidopsis, but the evolution of polycomb group gene families in monocots, particularly those with complex allopolyploid origins, is unknown. Results Here, we present the in silico identification of the Polycomb repressive complex 1 and 2 (PRC2, PRC1) subunits in allohexaploid bread wheat, the reconstruction of their evolutionary history and a transcriptional analysis over a series of 33 developmental stages. We identified four main subunits of PRC2 [E(z), Su(z), FIE and MSI] and three main subunits of PRC1 (Pc, Psc and Sce) and determined their chromosomal locations. We found that most of the genes coding for subunit proteins are present as paralogs in bread wheat. Using bread wheat RNA-seq data from different tissues and developmental stages throughout plant ontogenesis revealed variable transcriptional activity for individual paralogs. Phylogenetic analysis showed a high level of protein conservation among temperate cereals. Conclusions The identification and chromosomal location of the Polycomb repressive complex 1 and 2 core components in bread wheat may enable a deeper understanding of developmental processes, including vernalization, in commonly grown winter wheat.

scholarly journals Association of BMI1 with Polycomb Bodies Is Dynamic and Requires PRC2/EZH2 and the Maintenance DNA Methyltransferase DNMT1

2005 ◽  
Vol 25 (24) ◽  
pp. 11047-11058 ◽  
Author(s):  
Inmaculada Hernández-Muñoz ◽  
Panthea Taghavi ◽  
Coenraad Kuijl ◽  
Jacques Neefjes ◽  
Maarten van Lohuizen
Keyword(s):  
Dna Methyltransferase ◽  
Pericentric Heterochromatin ◽  
Polycomb Group ◽  
Gene Repression ◽  
Kinetic Properties ◽  
Polycomb Repressive Complex ◽  
Polycomb Repressive Complex 2 ◽  
Nuclear Structures ◽  
Stable Maintenance ◽  
Polycomb Bodies

ABSTRACT Polycomb group (PcG) proteins are epigenetic chromatin modifiers involved in heritable gene repression. Two main PcG complexes have been characterized. Polycomb repressive complex 2 (PRC2) is thought to be involved in the initiation of gene silencing, whereas Polycomb repressive complex 1 (PRC1) is implicated in the stable maintenance of gene repression. Here, we investigate the kinetic properties of the binding of one of the PRC1 core components, BMI1, with PcG bodies. PcG bodies are unique nuclear structures located on regions of pericentric heterochromatin, found to be the site of accumulation of PcG complexes in different cell lines. We report the presence of at least two kinetically different pools of BMI1, a highly dynamic and a less dynamic fraction, which may reflect BMI1 pools with different binding capacities to these stable heterochromatin domains. Interestingly, PRC2 members EED and EZH2 appear to be essential for BMI1 recruitment to the PcG bodies. Furthermore, we demonstrate that the maintenance DNA methyltransferase DNMT1 is necessary for proper PcG body assembly independent of DNMT-associated histone deacetylase activity. Together, these results provide new insights in the mechanism for regulation of chromatin silencing by PcG proteins and suggest a highly regulated recruitment of PRC1 to chromatin.

scholarly journals The genetic basis for PRC1 complex diversity emerged early in animal evolution

2020 ◽  
Vol 117 (37) ◽  
pp. 22880-22889 ◽  
Author(s):  
James M. Gahan ◽  
Fabian Rentzsch ◽  
Christine E. Schnitzler
Keyword(s):  
Classical Model ◽  
Ring Finger ◽  
Polycomb Group ◽  
Model Systems ◽  
Vertebrate Lineage ◽  
Animal Evolution ◽  
Chromatin Regulators ◽  
Core Components ◽  
Mammalian Counterpart ◽  
Polycomb Repressive Complex 1

Polycomb group proteins are essential regulators of developmental processes across animals. Despite their importance, studies on Polycomb are often restricted to classical model systems and, as such, little is known about the evolution of these important chromatin regulators. Here we focus on Polycomb Repressive Complex 1 (PRC1) and trace the evolution of core components of canonical and non-canonical PRC1 complexes in animals. Previous work suggested that a major expansion in the number of PRC1 complexes occurred in the vertebrate lineage. We show that the expansion of the Polycomb Group RING Finger (PCGF) protein family, an essential step for the establishment of the large diversity of PRC1 complexes found in vertebrates, predates the bilaterian–cnidarian ancestor. This means that the genetic repertoire necessary to form all major vertebrate PRC1 complexes emerged early in animal evolution, over 550 million years ago. We further show that PCGF5, a gene conserved in cnidarians and vertebrates but lost in all other studied groups, is expressed in the nervous system in the sea anemone Nematostella vectensis, similar to its mammalian counterpart. Together this work provides a framework for understanding the evolution of PRC1 complex diversity and it establishes Nematostella as a promising model system in which the functional ramifications of this diversification can be further explored.

scholarly journals Analysis of In-Vivo LacR-Mediated Gene Repression Based on the Mechanics of DNA Looping

PLoS ONE ◽  
2006 ◽  
Vol 1 (1) ◽  
pp. e136 ◽  
Author(s):  
Yongli Zhang ◽  
Abbye E. McEwen ◽  
Donald M. Crothers ◽  
Stephen D. Levene
Keyword(s):  
Dna Looping ◽  
Gene Repression

scholarly journals Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes

2011 ◽  
Vol 434 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Gaylor Boulay ◽  
Claire Rosnoblet ◽  
Cateline Guérardel ◽  
Pierre-Olivier Angrand ◽  
Dominique Leprince
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Protein Complexes ◽  
Functional Characterization ◽  
Polycomb Group ◽  
Phd Finger ◽  
Reverse Transcription Pcr ◽  
Tudor Domain ◽  
Self Association ◽  
Polycomb Repressive Complex 1

PcG (Polycomb group) proteins are conserved transcriptional repressors essential to regulate cell fate and to maintain epigenetic cellular memory. They work in concert through two main families of chromatin-modifying complexes, PRC1 (Polycomb repressive complex 1) and PRC2–4. In Drosophila, PRC2 contains the H3K27 histone methyltransferase E(Z) whose trimethylation activity towards PcG target genes is stimulated by PCL (Polycomb-like). In the present study, we have examined hPCL3, one of its three human paralogues. Through alternative splicing, hPCL3 encodes a long isoform, hPCL3L, containing an N-terminal TUDOR domain and two PHDs (plant homeodomains) and a smaller isoform, hPCL3S, lacking the second PHD finger (PHD2). By quantitative reverse transcription–PCR analyses, we showed that both isoforms are widely co-expressed at high levels in medulloblastoma. By co-immunoprecipitation analyses, we demonstrated that both isoforms interact with EZH2 through their common TUDOR domain. However, the hPCL3L-specific PHD2 domain, which is better conserved than PHD1 in the PCL family, is also involved in this interaction and implicated in the self-association of hPCL3L. Finally, we have demonstrated that both hPCL3 isoforms are physically associated with EZH2, but in different complexes. Our results provide the first evidence that the two hPCL3 isoforms belong to different complexes and raise important questions about their relative functions, particularly in tumorigenesis.

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