Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA149565 | ENA |
REPOSITORIES: ENA
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Project description:Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression. Microarray analysis of dKDM2, dRING, PC, PH and PSC target genes in Drosophila S2 cells Expression profiles of Drosophila S2 cells RNAi depleted (KD) for dKDM2, dRING, PC, PH or PSC were compared with expression profile of untreated S2 cells (Mock)
2011-12-13 | E-GEOD-34390 | biostudies-arrayexpress
Project description:Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factors (dRAF), a novel Polycomb group (PcG) silencing complex harboring the histone H2A ubiquitin ligase dRING, PSC and the F-box protein, and demethylase dKDM2. In vivo, dKDM2 shares many transcriptional targets with Polycomb and counteracts the histone methyltransferases TRX and ASH1. Importantly, cellular depletion and in vitro reconstitution assays revealed that dKDM2 not only mediates H3K36me2 demethylation but is also required for efficient H2A ubiquitylation by dRING/PSC. Thus, dRAF removes an active mark from histone H3 and adds a repressive one to H2A. These findings reveal coordinate trans-histone regulation by a PcG complex to mediate gene repression. Microarray analysis of dKDM2, dRING, PC, PH and PSC target genes in Drosophila S2 cells
2011-12-13 | GSE34390 | GEO
Project description:NguyenLK2011 - Ubiquitination dynamics in
Ring1B-Bmi1 system
This theoretical model investigates the
dynamics of Ring1B/Bmi1 ubiquitination to identify bistable
switch-like and oscillatory behaviour in the
system. Michaelis-Menten (MM) equations are used to formulate
the model. However, the authors show that the dynamics persist even
for Mass-Action kinetics. This SBML file is the MM version of the
model.
This model is described in the article:
Switches,
excitable responses and oscillations in the Ring1B/Bmi1
ubiquitination system.
Nguyen LK, Muñoz-García J,
Maccario H, Ciechanover A, Kolch W, Kholodenko BN.
PLoS Comput. Biol. 2011 Dec; 7(12):
e1002317
Abstract:
In an active, self-ubiquitinated state, the Ring1B ligase
monoubiquitinates histone H2A playing a critical role in
Polycomb-mediated gene silencing. Following ubiquitination by
external ligases, Ring1B is targeted for proteosomal
degradation. Using biochemical data and computational modeling,
we show that the Ring1B ligase can exhibit abrupt switches,
overshoot transitions and self-perpetuating oscillations
between its distinct ubiquitination and activity states. These
different Ring1B states display canonical or multiply branched,
atypical polyubiquitin chains and involve association with the
Polycomb-group protein Bmi1. Bistable switches and oscillations
may lead to all-or-none histone H2A monoubiquitination rates
and result in discrete periods of gene (in)activity. Switches,
overshoots and oscillations in Ring1B catalytic activity and
proteosomal degradation are controlled by the abundances of
Bmi1 and Ring1B, and the activities and abundances of external
ligases and deubiquitinases, such as E6-AP and USP7.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000622.
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To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000622 | BioModels
Project description:Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We describe the enrichment of H2A ubiquitylation at high density CpG promoters and provide evidence to suggest that DNA methylation may be linked to uH2A at these regions. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells. Keywords: Epigenetics Examination of uH2A binding in WT and Bmi1 null MEF cells.
2009-05-20 | E-GEOD-15896 | biostudies-arrayexpress
Project description:Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We describe the enrichment of H2A ubiquitylation at high density CpG promoters and provide evidence to suggest that DNA methylation may be linked to uH2A at these regions. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells. Keywords: Epigenetics
2009-05-20 | GSE15896 | GEO
Project description:Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome wide localization of uH2A. Using the recently developed ChIP-Seq technology, here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We provide evidence to suggest that DNA methylation is tightly linked to H2A ubiquitylation in high density CpG promoters. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells. Experiment Overall Design: RNA was extracted from wild-type MEF cells which were immortalized through TBX2 overexpression, amplified, labeled, and hybridized to an Affymetrix 430 2 microarray. In parallel, RNA was prepared from TBX2-immortalized Bmi1 null MEF cells and hybridized to an Affymetrix 430 2 microarray.
2009-05-11 | E-GEOD-15715 | biostudies-arrayexpress
Project description:Drosophila Haspin kinase phosphorylates Histone H3 at threonine 3 at centromeric heterochromatin and either lamin- or polycomb-enriched euchromatic regions, being required for nuclear organization of interphase cells and polycomb-dependent gene silencing.
2020-08-07 | GSE98223 | GEO
Project description:The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2). PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC1. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. Experiment Overall Design: Eed is a protein included in PRC2 (Polycomb repressor complex). Experiment Overall Design: We generated constitutive Eed KO mouse ES cells and observed gene expression using Affymetrix MOE430.2 microarray. Experiment Overall Design: These results were compared with other KO cells of PRC1 proteins (Ring1A, Ring1B) and other proteins in our study.
2008-04-07 | E-GEOD-10574 | biostudies-arrayexpress
Project description:The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2)1-5. PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC13-7. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog9. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. Experiment Overall Design: These experiments were designed to investigate how gene expression would be affected in the absence of Oct3/4 in mouse ES cells. Because constitutive Oct3/4 KO cells are not maintained, we generated conditional KO cells.
2008-04-07 | E-GEOD-10477 | biostudies-arrayexpress
Project description:The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2)1-5. PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC13-7. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog9. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. Experiment Overall Design: Gene expression in Dnmt1-KO cells were observed using Affymetrix chip: MOE 430 2.0. Experiment Overall Design: These experiments were performed to obtain control of KO cells for other experiments that affect stem cell differentiation.
2008-04-07 | E-GEOD-10519 | biostudies-arrayexpress