scholarly journals Genome-wide Prediction of Potential Polycomb Response Elements and their Functions

2019 ◽  
Author(s):  
Morteza Khabiri ◽  
Peter L. Freddolino
Keyword(s):  
Binding Sites ◽  
High Performance ◽  
Machine Learning Algorithms ◽  
Polycomb Group ◽  
Entire Genome ◽  
Trithorax Group ◽  
Response Elements ◽  
Associated Proteins ◽  
Polycomb Response Elements ◽  
Trithorax Group Proteins

AbstractThe Polycomb-group proteins (PcG) and Trithorax-group proteins (TrxG) are two major epigenetic regulators important for proper differentiation during development (1, 2). In Drosophila melanogaster (D. melanogaster), Polycomb response elements (PREs) are short segments of DNA with a high density of binding sites for transcription factors (TFs) that recruit PcG and TrxG proteins to chromatin. Each PRE has a different number of binding sites for PcG and TrxG, and these binding sites have different topological organizations. It is thus difficult to find general rules to discover the locations of PREs over the entire genome. We have developed a framework to predict the locations and roles of potential PRE regions over the entire D. melanogaster genome using machine learning algorithms. Using a combination of motif-based and simple sequence-based features, we were able to train a random forest (RF) model with very high performance in predicting active PRE regions. This model could distinguish potential PRE regions from non-PRE regions (precision and recall ~0.92 upon cross-validation). In the process, the model suggests that previously unrecognized TFs might contribute to PcG/TrxG recruitment at the PRE locations, as the presence of binding sites for those factors is strongly informative of active PREs. A secondary regression model provides information on features that further differentiate PREs into functional subclasses. Our findings provide both new predictions of 7887 potential PREs in the D. melanogaster genome, and new mechanistic insight into the set of DNA-associated proteins that may contribute to PcG recruitment and/or activity.

scholarly journals Recruitment of components of Polycomb Group chromatin complexes in Drosophila

Development ◽  
2001 ◽  
Vol 128 (1) ◽  
pp. 75-85 ◽  
Author(s):  
S. Poux ◽  
D. McCabe ◽  
V. Pirrotta
Keyword(s):  
Binding Sites ◽  
Imaginal Discs ◽  
Polycomb Group ◽  
Dna Binding Domain ◽  
Response Elements ◽  
Nuclear Extracts ◽  
Polycomb Response Elements ◽  
Polycomb Group Complexes ◽  
State Of Activity

Polycomb Group complexes assemble at polycomb response elements (PREs) in vivo and silence genes in the surrounding chromatin. To study the recruitment of silencing complexes, we have targeted various Polycomb Group (PcG) proteins by fusing them to the LexA DNA binding domain. When LexA-PC, -PSC, -PH or -SU(Z)2 are targeted to a reporter gene, they recruit functional PcG-silencing complexes that recapitulate the silencing behavior of a PRE: silencing is sensitive to the state of activity of the target chromatin. When the target is transcriptionally active, silencing is not established but when the target is not active at syncytial blastoderm, it becomes silenced. The repressed state persists through embryonic development but cannot be maintained in larval imaginal discs even when the LexA-PcG fusion is constitutively expressed, suggesting a discontinuity in the mechanism of repression. These proteins also interact with other PC-containing complexes in embryonic nuclear extracts. In contrast LexA-PHO is neither able to silence nor to interact with PC-containing complexes. Analysis of pho mutant embryos and of PRE constructs whose PHO-binding sites are mutated suggests that, while PHO is important for silencing in imaginal discs, it is not necessary for embryonic PcG silencing.

scholarly journals Combgap contributes to recruitment of Polycomb group proteins in Drosophila

2016 ◽  
Vol 113 (14) ◽  
pp. 3826-3831 ◽  
Author(s):  
Payal Ray ◽  
Sandip De ◽  
Apratim Mitra ◽  
Karel Bezstarosti ◽  
Jeroen A. A. Demmers ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Sites ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Polycomb Group ◽  
Developmentally Regulated ◽  
Polycomb Response Elements ◽  
Protein Recruitment ◽  
Polycomb Repressive Complex 1 ◽  
Transcriptional State

Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as “Polycomb response elements” (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.

scholarly journals Evolution of Polycomb-group function in the green lineage

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 268 ◽  
Author(s):  
Daniel Schubert
Keyword(s):  
Land Plant ◽  
Plant Evolution ◽  
Polycomb Group ◽  
Protein Activity ◽  
Group Function ◽  
Trithorax Group ◽  
Polycomb Repressive Complex 2 ◽  
Associated Proteins ◽  
Land Plant Evolution ◽  
Green Lineage

Epigenetic gene regulation ensures the mitotically or meiotically stable heritability (or both) of gene expression or protein activity states and maintains repetitive element repression and cellular identities. The repressive Polycomb-group (PcG) proteins consist of several large complexes that control cellular memory by acting on chromatin and are antagonized by the Trithorax-group proteins. Especially, Polycomb repressive complex 2 (PRC2) is highly conserved in plants and animals but its function in unicellular eukaryotes and during land plant evolution is less understood. Additional PcG complexes and associated proteins are only partially conserved and have evolved in a lineage-specific manner. In this review, I will focus on recent advances in the understanding of PcG function in the green lineage and its contribution to land plant evolution.

TheDrosophilaTrithorax protein is a coactivator required to prevent re-establishment of Polycomb silencing

Development ◽  
2002 ◽  
Vol 129 (10) ◽  
pp. 2483-2493 ◽  
Author(s):  
Sylvain Poux ◽  
Béatrice Horard ◽  
Christian J. A. Sigrist ◽  
Vincenzo Pirrotta
Keyword(s):  
Imaginal Discs ◽  
Polycomb Group ◽  
Active State ◽  
Homeotic Genes ◽  
Epigenetic Memory ◽  
Gaga Factor ◽  
Response Elements ◽  
Active Gene ◽  
Polycomb Response Elements

Polycomb group (PcG) and Trithorax (TRX) complexes assemble at Polycomb response elements (PREs) and maintain respectively the repressed and active state of homeotic genes. Although PcG and TRX complexes are distinct, their binding to some PRE fragments in vitro depends on GAGA motifs. GAGA factor immunoprecipitates with both complexes. In presence of a PRE, TRX stimulates expression and prevents the return of repression at later stages. When TRX levels are reduced, repression is re-established in inappropriate regions of imaginal discs, suggesting that TRX insufficiency impairs the epigenetic memory of the active state. Targeting a GAL-TRX fusion shows that TRX is a coactivator that stimulates expression of an active gene but cannot initiate expression by itself. Targeting a histone acetylase to a PRE does not affect embryonic silencing but causes a loss of memory in imaginal discs, suggesting that deacetylation is required to establish the memory of the repressed state.

scholarly journals The Mcp Element From the Drosophila melanogaster Bithorax Complex Mediates Long-Distance Regulatory Interactions

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1333-1356 ◽  
Author(s):  
Martin Muller ◽  
Kirsten Hagstrom ◽  
Henrik Gyurkovics ◽  
Vincenzo Pirrotta ◽  
Paul Schedl
Keyword(s):  
Drosophila Melanogaster ◽  
Polycomb Group ◽  
Small Fragment ◽  
Bithorax Complex ◽  
Long Distance ◽  
Response Elements ◽  
Regulatory Interactions ◽  
Homolog Pairing ◽  
Polycomb Response Elements ◽  
Trans Regulation

Abstract In the studies reported here, we have examined the properties of the Mcp element from the Drosophila melanogaster bithorax complex (BX-C). We have found that sequences from the Mcp region of BX-C have properties characteristic of Polycomb response elements (PREs), and that they silence adjacent reporters by a mechanism that requires trans-interactions between two copies of the transgene. However, Mcp trans-regulatory interactions have several novel features. In contrast to classical transvection, homolog pairing does not seem to be required. Thus, trans-regulatory interactions can be observed not only between Mcp transgenes inserted at the same site, but also between Mcp transgenes inserted at distant sites on the same chromosomal arm, or even on different arms. Trans-regulation can even be observed between transgenes inserted on different chromosomes. A small 800-bp Mcp sequence is sufficient to mediate these long-distance trans-regulatory interactions. This small fragment has little silencing activity on its own and must be combined with other Polycomb-Group-responsive elements to function as a “pairing-sensitive” silencer. Finally, this pairing element can also mediate long-distance interactions between enhancers and promoters, activating mini-white expression.

scholarly journals Three classes of response elements for human PRC2 and MLL1/2-trithorax complexes

2017 ◽  
Author(s):  
Junqing Du ◽  
Brian Kirk ◽  
Jia Zeng ◽  
Jianpeng Ma ◽  
Qinghua Wang
Keyword(s):  
Target Genes ◽  
Cpg Islands ◽  
Embryonic Stem ◽  
Polycomb Group ◽  
Epigenetic Memory ◽  
Trithorax Group ◽  
Response Elements ◽  
Differentiated Cells ◽  
Dna Elements ◽  
First Time

SummaryPolycomb group (PcG) and trithorax group (TrxG) proteins are essential for maintaining epigenetic memory in both embryonic stem cells and differentiated cells. To date, how they are localized to hundreds of specific target genes within a vertebrate genome had remained elusive. Here, by focusing on short cis-acting DNA elements of single functions, we discovered, for the first time, to our knowledge, three classes of response elements in human genome: PcG response elements (PREs), MLL1/2-TrxG response elements (TREs) and PcG/TrxG response elements (P/TREs). We further demonstrated that, in contrast to their proposed roles in recruiting PcG proteins to PREs, YY1 and CpG islands are specifically enriched in TREs and P/TREs, but not in PREs. The three classes of response elements as unraveled in this study open new doors for a deeper understanding of PcG and TrxG mechanisms in vertebrates.

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