oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
The Enhancer of Trithorax and Polycomb Corto Interacts with Cyclin G in Drosophila  [PDF]
Juliette Salvaing, Anja C. Nagel, Emmanuèle Mouchel-Vielh, Sébastien Bloyer, Dieter Maier, Anette Preiss, Frédérique Peronnet
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001658
Abstract: Background Polycomb (PcG) and trithorax (trxG) genes encode proteins involved in the maintenance of gene expression patterns, notably Hox genes, throughout development. PcG proteins are required for long-term gene repression whereas TrxG proteins are positive regulators that counteract PcG action. PcG and TrxG proteins form large complexes that bind chromatin at overlapping sites called Polycomb and Trithorax Response Elements (PRE/TRE). A third class of proteins, so-called “Enhancers of Trithorax and Polycomb” (ETP), interacts with either complexes, behaving sometimes as repressors and sometimes as activators. The role of ETP proteins is largely unknown. Methodology/Principal Findings In a two-hybrid screen, we identified Cyclin G (CycG) as a partner of the Drosophila ETP Corto. Inactivation of CycG by RNA interference highlights its essential role during development. We show here that Corto and CycG directly interact and bind to each other in embryos and S2 cells. Moreover, CycG is targeted to polytene chromosomes where it co-localizes at multiple sites with Corto and with the PcG factor Polyhomeotic (PH). We observed that corto is involved in maintaining Abd-B repression outside its normal expression domain in embryos. This could be achieved by association between Corto and CycG since both proteins bind the regulatory element iab-7 PRE and the promoter of the Abd-B gene. Conclusions/Significance Our results suggest that CycG could regulate the activity of Corto at chromatin and thus be involved in changing Corto from an Enhancer of TrxG into an Enhancer of PcG.
Functional Anatomy of Polycomb and Trithorax Chromatin Landscapes in Drosophila Embryos  [PDF]
Bernd Schuettengruber,Mythily Ganapathi,Benjamin Leblanc,Manuela Portoso,Rami Jaschek,Bas Tolhuis,Maarten van Lohuizen,Amos Tanay,Giacomo Cavalli
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000013
Abstract: Polycomb group (PcG) and trithorax group (trxG) proteins are conserved chromatin factors that regulate key developmental genes throughout development. In Drosophila, PcG and trxG factors bind to regulatory DNA elements called PcG and trxG response elements (PREs and TREs). Several DNA binding proteins have been suggested to recruit PcG proteins to PREs, but the DNA sequences necessary and sufficient to define PREs are largely unknown. Here, we used chromatin immunoprecipitation (ChIP) on chip assays to map the chromosomal distribution of Drosophila PcG proteins, the N- and C-terminal fragments of the Trithorax (TRX) protein and four candidate DNA-binding factors for PcG recruitment. In addition, we mapped histone modifications associated with PcG-dependent silencing and TRX-mediated activation. PcG proteins colocalize in large regions that may be defined as polycomb domains and colocalize with recruiters to form several hundreds of putative PREs. Strikingly, the majority of PcG recruiter binding sites are associated with H3K4me3 and not with PcG binding, suggesting that recruiter proteins have a dual function in activation as well as silencing. One major discriminant between activation and silencing is the strong binding of Pleiohomeotic (PHO) to silenced regions, whereas its homolog Pleiohomeotic-like (PHOL) binds preferentially to active promoters. In addition, the C-terminal fragment of TRX (TRX-C) showed high affinity to PcG binding sites, whereas the N-terminal fragment (TRX-N) bound mainly to active promoter regions trimethylated on H3K4. Our results indicate that DNA binding proteins serve as platforms to assist PcG and trxG binding. Furthermore, several DNA sequence features discriminate between PcG- and TRX-N–bound regions, indicating that underlying DNA sequence contains critical information to drive PREs and TREs towards silencing or activation.
Functional Anatomy of Polycomb and Trithorax Chromatin Landscapes in Drosophila Embryos  [PDF]
Bernd Schuettengruber equal contributor,Mythily Ganapathi equal contributor,Benjamin Leblanc,Manuela Portoso,Rami Jaschek,Bas Tolhuis,Maarten van Lohuizen,Amos Tanay,Giacomo Cavalli
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000013
Abstract: Polycomb group (PcG) and trithorax group (trxG) proteins are conserved chromatin factors that regulate key developmental genes throughout development. In Drosophila, PcG and trxG factors bind to regulatory DNA elements called PcG and trxG response elements (PREs and TREs). Several DNA binding proteins have been suggested to recruit PcG proteins to PREs, but the DNA sequences necessary and sufficient to define PREs are largely unknown. Here, we used chromatin immunoprecipitation (ChIP) on chip assays to map the chromosomal distribution of Drosophila PcG proteins, the N- and C-terminal fragments of the Trithorax (TRX) protein and four candidate DNA-binding factors for PcG recruitment. In addition, we mapped histone modifications associated with PcG-dependent silencing and TRX-mediated activation. PcG proteins colocalize in large regions that may be defined as polycomb domains and colocalize with recruiters to form several hundreds of putative PREs. Strikingly, the majority of PcG recruiter binding sites are associated with H3K4me3 and not with PcG binding, suggesting that recruiter proteins have a dual function in activation as well as silencing. One major discriminant between activation and silencing is the strong binding of Pleiohomeotic (PHO) to silenced regions, whereas its homolog Pleiohomeotic-like (PHOL) binds preferentially to active promoters. In addition, the C-terminal fragment of TRX (TRX-C) showed high affinity to PcG binding sites, whereas the N-terminal fragment (TRX-N) bound mainly to active promoter regions trimethylated on H3K4. Our results indicate that DNA binding proteins serve as platforms to assist PcG and trxG binding. Furthermore, several DNA sequence features discriminate between PcG- and TRX-N–bound regions, indicating that underlying DNA sequence contains critical information to drive PREs and TREs towards silencing or activation.
Functional Conservation of Asxl2, a Murine Homolog for the Drosophila Enhancer of Trithorax and Polycomb Group Gene Asx  [PDF]
Heather A. Baskind, Lucy Na, Quanhong Ma, Mayur P. Patel, David L. Geenen, Q. Tian Wang
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004750
Abstract: Background Polycomb-group (PcG) and trithorax-group (trxG) proteins regulate histone methylation to establish repressive and active chromatin configurations at target loci, respectively. These chromatin configurations are passed on from mother to daughter cells, thereby causing heritable changes in gene expression. The activities of PcG and trxG proteins are regulated by a special class of proteins known as Enhancers of trithorax and Polycomb (ETP). The Drosophila gene Additional sex combs (Asx) encodes an ETP protein and mutations in Asx enhance both PcG and trxG mutant phenotypes. The mouse and human genomes each contain three Asx homologues, Asx-like 1, 2, and 3. In order to understand the functions of mammalian Asx-like (Asxl) proteins, we generated an Asxl2 mutant mouse from a gene-trap ES cell line. Methodology/Principal Findings We show that the Asxl2 gene trap is expressed at high levels in specific tissues including the heart, the axial skeleton, the neocortex, the retina, spermatogonia and developing oocytes. The gene trap mutation is partially embryonic lethal and approximately half of homozygous animals die before birth. Homozygotes that survive embryogenesis are significantly smaller than controls and have a shortened life span. Asxl2?/? mice display both posterior transformations and anterior transformation in the axial skeleton, suggesting that the loss of Asxl2 disrupts the activities of both PcG and trxG proteins. The PcG-associated histone modification, trimethylation of histone H3 lysine 27, is reduced in Asxl2?/? heart. Necropsy and histological analysis show that mutant mice have enlarged hearts and may have impaired heart function. Conclusions/Significance Our results suggest that murine Asxl2 has conserved ETP function and plays dual roles in the promotion of PcG and trxG activity. We have also revealed an unexpected role for Asxl2 in the heart, suggesting that the PcG/trxG system may be involved in the regulation of cardiac function.
Stability and Dynamics of Polycomb Target Sites in Drosophila Development  [PDF]
Camilla Kwong equal contributor,Boris Adryan equal contributor,Ian Bell,Lisa Meadows,Steven Russell,J. Robert Manak,Robert White
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000178
Abstract: Polycomb-group (PcG) and Trithorax-group proteins together form a maintenance machinery that is responsible for stable heritable states of gene activity. While the best-studied target genes are the Hox genes of the Antennapedia and Bithorax complexes, a large number of key developmental genes are also Polycomb (Pc) targets, indicating a widespread role for this maintenance machinery in cell fate determination. We have studied the linkage between the binding of PcG proteins and the developmental regulation of gene expression using whole-genome mapping to identify sites bound by the PcG proteins, Pc and Pleiohomeotic (Pho), in the Drosophila embryo and in a more restricted tissue, the imaginal discs of the third thoracic segment. Our data provide support for the idea that Pho is a general component of the maintenance machinery, since the majority of Pc targets are also associated with Pho binding. We find, in general, considerable developmental stability of Pc and Pho binding at target genes and observe that Pc/Pho binding can be associated with both expressed and inactive genes. In particular, at the Hox complexes, both active and inactive genes have significant Pc and Pho binding. However, in comparison to inactive genes, the active Hox genes show reduced and altered binding profiles. During development, Pc target genes are not simply constantly associated with Pc/Pho binding, and we identify sets of genes with clear differential binding between embryo and imaginal disc. Using existing datasets, we show that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding. Overall, our analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription. Pc/Pho binding does not preclude transcription, but levels of Pc/Pho binding change during development, and loss of Pc/Pho binding can be associated with both stable gene activity and inactivity.
Coordinated regulation of Myc trans-activation targets by Polycomb and the Trithorax group protein Ash1
Julie M Goodliffe, Michael D Cole, Eric Wieschaus
BMC Molecular Biology , 2007, DOI: 10.1186/1471-2199-8-40
Abstract: To identify chromatin binding proteins with a potential role in controlling Myc activity, we established a genetic assay for dMyc activity in Drosophila. We conducted a genome-wide screen using this assay, and identified the Trithorax Group protein Ash1 as a modifier of dMyc activity. Ash1 is a histone methyltransferase known for its role in opposing repression by Polycomb. Using RNAi in the embryo and Affymetrix microarrays, we show that ash1 RNAi causes the increased expression of many genes, suggesting that it is directly or indirectly required for repression in the embryo, in contrast to its known role in maintenance of activation. Many of these genes also respond similarly upon depletion of Pc and pho transcripts, as determined by concurrent microarray analysis of Pc and pho RNAi embryos, suggesting that the three are required for low levels of expression of a common set of targets. Further, many of these overlapping targets are also activated by Myc overexpression. We identify a second group of genes whose expression in the embryo requires Ash1, consistent with its previously established role in maintenance of activation. We find that this second group of Ash1 targets overlaps those activated by Myc and that ectopic Myc overcomes their requirement for Ash1.Genetic, genomic and chromatin immunoprecipitation data suggest a model in which Pc, Ash1 and Pho are required to maintain a low level of expression of embryonic targets of activation by Myc, and that this occurs, directly or indirectly, by a combination of disparate chromatin modifications.Cancer can arise in many ways, one of the most potent being deregulation of the myc proto-oncogene. Myc is a transcription factor, and its C-terminal domain is required for dimerization with its partner Max and its subsequent binding to DNA. It also possesses an N-terminal trans-activation domain that is required for both Myc's biological activities of transcriptional activation and repression. Activation by Myc involves
New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts with Methylated Ribosomal Protein L12 Via Its Chromodomain  [PDF]
Anne Coléno-Costes,Suk Min Jang,Augustin de Vanssay,Julien Rougeot,Tahar Bouceba,Neel B. Randsholt,Jean-Michel Gibert,Stéphane Le Crom,Emmanuèle Mouchel-Vielh,Sébastien Bloyer equal contributor,Frédérique Peronnet equal contributor
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1003006
Abstract: Chromodomains are found in many regulators of chromatin structure, and most of them recognize methylated lysines on histones. Here, we investigate the role of the Drosophila melanogaster protein Corto's chromodomain. The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activation of gene expression. Over-expression of the Corto chromodomain (CortoCD) in transgenic flies shows that it is a chromatin-targeting module, critical for Corto function. Unexpectedly, mass spectrometry analysis reveals that polypeptides pulled down by CortoCD from nuclear extracts correspond to ribosomal proteins. Furthermore, real-time interaction analyses demonstrate that CortoCD binds with high affinity RPL12 tri-methylated on lysine 3. Corto and RPL12 co-localize with active epigenetic marks on polytene chromosomes, suggesting that both are involved in fine-tuning transcription of genes in open chromatin. RNA–seq based transcriptomes of wing imaginal discs over-expressing either CortoCD or RPL12 reveal that both factors deregulate large sets of common genes, which are enriched in heat-response and ribosomal protein genes, suggesting that they could be implicated in dynamic coordination of ribosome biogenesis. Chromatin immunoprecipitation experiments show that Corto and RPL12 bind hsp70 and are similarly recruited on gene body after heat shock. Hence, Corto and RPL12 could be involved together in regulation of gene transcription. We discuss whether pseudo-ribosomal complexes composed of various ribosomal proteins might participate in regulation of gene expression in connection with chromatin regulators.
Corto and DSP1 interact and bind to a maintenance element of the Scr Hox gene: understanding the role of Enhancers of trithorax and Polycomb
Juliette Salvaing, Martine Decoville, Emmanuèle Mouchel-Vielh, Marianne Bussière, Anne Daulny, Lidiya Boldyreva, Igor Zhimulev, Daniel Locker, Frédérique Peronnet
BMC Biology , 2006, DOI: 10.1186/1741-7007-4-9
Abstract: We show that Corto and DSP1 proteins co-localize at 91 sites on polytene chromosomes and co-immunoprecipitate in embryos. They interact directly through the DSP1 HMG-boxes and the amino-part of Corto, which contains a chromodomain. In order to search for a common target, we performed a genetic interaction analysis. We observed that corto mutants suppressed dsp11 sex comb phenotypes and enhanced AntpScx phenotypes, suggesting that corto and dsp1 are simultaneously involved in the regulation of Scr. Using chromatin immunoprecipitation of the Scr ME, we found that Corto was present on this ME both in Drosophila S2 cells and in embryos, whereas DSP1 was present only in S2 cells.Our results reveal that the proteins Corto and DSP1 are differently recruited to a Scr ME depending on whether the ME is active, as seen in S2 cells, or inactive, as in most embryonic cells. The presence of a given combination of ETPs on an ME would control the recruitment of either PcG or TrxG complexes, propagating the silenced or active state.Many transcription factors are expressed only transiently during development. After they have disappeared, the patterns of gene expression they have induced must be inherited by daughter cells. In eukaryotes, two groups of proteins, the Polycomb-group (PcG) and the Trithorax-group (TrxG), fulfil this memory function. Their existence was first revealed in Drosophila melanogaster where homeotic gene (Hox) expression is established in early embryos by the transient Gap and Pair-Rule transcription factors and controlled by PcG and TrxG proteins during the rest of development [1-3]. The PcG and TrxG proteins combine into several heteromeric complexes that bind chromatin. PcG complexes maintain Hox gene silencing whereas TrxG complexes counteract the action of PcG complexes (reviewed in [4]). These proteins regulate many other genes such as engrailed [5,6], ph [7], fork head [8] and the iroquois-complex [9].In Drosophila, at least two PcG complexes called PRC2
Leptin Signaling Modulates Expression of Polycomb and Trithorax Complexes in the Brain of Fat Tissue Implanted Polycystic Ovarian Sindrome Mice  [PDF]
Eduardo Henrique da Silva Freitas, Samuel Marcos Ribeiro de Noronha, Maria Nazareth Gamboa Ritto, Carlos Fernandes Baptista, Ismael Dale Cotrim Guerreiro da Silva, Silvana Aparecida Alves Correa-Noronha, Ivaldo da Silva
American Journal of Molecular Biology (AJMB) , 2014, DOI: 10.4236/ajmb.2014.44020
Abstract: The Polycystic Ovary Syndrome (PCOS) is the most common androgenic disorder in women during reproductive life. PCOS may also be accompanied by metabolic syndrome and recent studies point to leptin as playing a role in disrupting infertility and in changing the energy balance in obese mice through its action on the hypothalamus. The aim is to assess the expression of the Polycomb & Trithorax Complexes genes in brain of mice transplanted with fat tissue from normal mice, in order to better understand the neuronal mechanisms underlying the reversion of PCOS. Three B6 V-Lepob/J mouse groups: Normal weight, obese and seven-day-treatment obese had their brain RNA extracted and submitted to an 84 Polycomb & Trithorax Complexes genes PCR Array plate and MetacoreTM pathways localization. Genomic profiles obtained were compared to the ones of the normal-weight-mice group. Differentially expressed genes were 13% and 26% respectively to control and treatment. Major changes were in genes: Snai1/31; Smarca1/?17; Dnmt3b/4.7; Ezh1/ 15. Altered genes were associated to canonical pathways and provided 3 networks related to epigenetics. Underlying neuronal changes caused by leptin in obese mice brain, there is an important role being played by the histone code. Here there is evidence that leptin drives the chromatin packing to a more condensed pattern. Upregulation of methyltransferase genes, like Ezh1, favors this thought. In summary the Polycomb & Trithorax complexes might answer for the silencing of some downregulated genes in the obese mice brain when exposed to leptin.
Phenotypic Plasticity of the Drosophila Transcriptome  [PDF]
Shanshan Zhou,Terry G. Campbell,Eric A. Stone,Trudy F. C. Mackay,Robert R. H. Anholt
PLOS Genetics , 2012, DOI: 10.1371/journal.pgen.1002593
Abstract: Phenotypic plasticity is the ability of a single genotype to produce different phenotypes in response to changing environments. We assessed variation in genome-wide gene expression and four fitness-related phenotypes of an outbred Drosophila melanogaster population under 20 different physiological, social, nutritional, chemical, and physical environments; and we compared the phenotypically plastic transcripts to genetically variable transcripts in a single environment. The environmentally sensitive transcriptome consists of two transcript categories, which comprise ~15% of expressed transcripts. Class I transcripts are genetically variable and associated with detoxification, metabolism, proteolysis, heat shock proteins, and transcriptional regulation. Class II transcripts have low genetic variance and show sexually dimorphic expression enriched for reproductive functions. Clustering analysis of Class I transcripts reveals a fragmented modular organization and distinct environmentally responsive transcriptional signatures for the four fitness-related traits. Our analysis suggests that a restricted environmentally responsive segment of the transcriptome preserves the balance between phenotypic plasticity and environmental canalization.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.