scholarly journals The H3K4 Demethylase Lid Associates with and Inhibits Histone Deacetylase Rpd3

2008 ◽  
Vol 29 (6) ◽  
pp. 1401-1410 ◽  
Author(s):  
Nara Lee ◽  
Hediye Erdjument-Bromage ◽  
Paul Tempst ◽  
Richard S. Jones ◽  
Yi Zhang
Keyword(s):  
Histone Deacetylase ◽  
Gene Activation ◽  
Polycomb Group ◽  
Genetic Classification ◽  
Trithorax Group ◽  
Nuclear Extracts ◽  
Demethylase Activity ◽  
Jmjc Domain ◽  
Active Transcription ◽  
Group Protein

ABSTRACT JmjC domain-containing proteins have been shown to possess histone demethylase activity. One of these proteins is the Drosophila histone H3 lysine 4 demethylase Little imaginal discs (Lid), which has been genetically classified as a Trithorax group protein. However, contrary to the supposed function of Lid in gene activation, the biochemical activity of this protein entails the removal of a histone mark that is correlated with active transcription. To understand the molecular mechanism behind the function of Lid, we have purified a Lid-containing protein complex from Drosophila embryo nuclear extracts. In addition to Lid, the complex contains Rpd3, CG3815/Drosophila Pf1, CG13367, and Mrg15. Rpd3 is a histone deacetylase, and along with Polycomb group proteins, which antagonize the function of Trithorax group proteins, it negatively regulates transcription. By reconstituting the Lid complex, we demonstrated that the demethylase activity of Lid is not affected by its association with other proteins. However, the deacetylase activity of Rpd3 is greatly diminished upon incorporation into the Lid complex. Thus, our finding that Lid antagonizes Rpd3 function provides an explanation for the genetic classification of Lid as a positive transcription regulator.

scholarly journals Polycomb Group and SCF Ubiquitin Ligases Are Found in a Novel BCOR Complex That Is Recruited to BCL6 Targets

2006 ◽  
Vol 26 (18) ◽  
pp. 6880-6889 ◽  
Author(s):  
Micah D. Gearhart ◽  
Connie M. Corcoran ◽  
Joseph A. Wamstad ◽  
Vivian J. Bardwell
Keyword(s):  
Transcriptional Repression ◽  
E3 Ligase ◽  
Ubiquitin Ligases ◽  
Polycomb Group ◽  
Fusion Partner ◽  
Ubiquitin E3 Ligase ◽  
Sex Combs ◽  
Demethylase Activity ◽  
Jmjc Domain ◽  
Mixed Lineage Leukemia Fusion

ABSTRACT The corepressor BCOR potentiates transcriptional repression by the proto-oncoprotein BCL6 and suppresses the transcriptional activity of a common mixed-lineage leukemia fusion partner, AF9. Mutations in human BCOR cause male lethal, X-linked oculofaciocardiodental syndrome. We identified a BCOR complex containing Polycomb group (PcG) and Skp-Cullin-F-box subcomplexes. The PcG proteins include RING1, RYBP, NSPC1, a Posterior Sex Combs homolog, and RNF2, an E3 ligase for the mono-ubiquitylation of H2A. BCOR complex components and mono-ubiquitylated H2A localize to BCL6 targets, indicating that the BCOR complex employs PcG proteins to expand the repertoire of enzymatic activities that can be recruited by BCL6. This also suggests that BCL6 can target PcG proteins to DNA. In addition, the BCOR complex contains components of a second ubiquitin E3 ligase, namely, SKP1 and FBXL10 (JHDM1B). We show that BCOR coimmunoprecipitates isoforms of FBXL10 which contain a JmjC domain that recently has been determined to have histone H3K36 demethylase activity. The recruitment of two distinct classes of E3 ubiquitin ligases and a histone demethylase by BCOR suggests that BCOR uses a unique combination of epigenetic modifications to direct gene silencing.

Histone H3K4 demethylases are essential in development and differentiationThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2007 ◽  
Vol 85 (4) ◽  
pp. 435-443 ◽  
Author(s):  
Elizaveta V. Benevolenskaya
Keyword(s):  
Cell Fate ◽  
Histone Methylation ◽  
Peer Review Process ◽  
Active Regions ◽  
Model Organisms ◽  
Global Changes ◽  
Histone Demethylases ◽  
Trithorax Group ◽  
Demethylase Activity ◽  
Jmjc Domain

Lysine histone methylation is one of the most robust epigenetic marks and is essential for the regulation of multiple cellular processes. The methylation of Lys4 of histone H3 seems to be of particular significance. It is associated with active regions of the genome, and in Drosophila it is catalyzed by trithorax-group proteins that have become paradigms of developmental regulators at the level of chromatin. Like other histone methylation events, H3K4 methylation was considered irreversible until the identification of a large number of histone demethylases indicated that demethylation events play an important role in histone modification dynamics. However, the described demethylases had no strictly assigned biological functions and the identity of the histone demethylases that would contribute to the epigenetic changes specifying certain biological processes was unknown. Recently, several groups presented evidence that a family of 4 JmjC domain proteins results in the global changes of histone demethylation, and in elegant studies using model organisms, they demonstrated the importance of this family of histone demethylases in cell fate determination. All 4 proteins possess the demethylase activity specific to H3K4 and belong to the poorly described JARID1 protein family.

Polycomb and Trithorax group protein-mediated control of stress responses in plants

2014 ◽  
Vol 395 (11) ◽  
pp. 1291-1300 ◽  
Author(s):  
Julia Anna Kleinmanns ◽  
Daniel Schubert
Keyword(s):  
Stress Responses ◽  
Current Knowledge ◽  
Epigenetic Inheritance ◽  
Polycomb Group ◽  
Gene Repression ◽  
Stable Gene ◽  
Trithorax Group ◽  
Stress Memory ◽  
Group Protein

Abstract A plant’s experience of abiotic or biotic stress can lead to stress memory in order to react faster and more efficiently to subsequent stresses. Molecularly, the memory of a stress can rely on stable inheritance through mitotic and meiotic cell divisions, thus epigenetic inheritance. The key epigenetic regulators are DNA cytosine methyltransferases and the Polycomb group (PcG) and Trithorax group (TrxG) proteins, which control numerous developmental processes. PcG and TrxG proteins act antagonistically on stable gene repression through mediating trimethylation of histone H3 lysine 27 (H3K27me3) and H3K4me3, respectively, and target thousands of genes in plants, including many genes responsive to stress. The role of PcG/TrxG proteins in regulating stress responses and memory, however, is just emerging. While it is well investigated that stress can induce changes of histone modifications at genes regulated by stress, it is largely unclear whether these changes are mitotically and/or meiotically heritable, hence confer somatic and/or transgenerational stress memory. As the literature on the role of DNA methylation in regulating stress responses has recently been extensively summarized, we focus this review on the current knowledge on the role of PcG and TrxG in stress responses and memory.

scholarly journals Molecular Genetic Analysis of Drosophila ash2, a Member of the Trithorax Group Required for Imaginal Disc Pattern Formation

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 621-633 ◽  
Author(s):  
Amy L Adamson ◽  
Allen Shearn
Keyword(s):  
Pattern Formation ◽  
Fat Body ◽  
Polyclonal Antibodies ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Polycomb Group ◽  
Trithorax Group ◽  
Phd Finger ◽  
Reading Frame ◽  
Active Transcription

Abstract The ash2 gene is a member of the trithorax group of genes whose products function to maintain active transcription of homeotic selector genes. Mutations in ash2 cause the homeotic transformations expected for a gene in this group but, in addition, cause a variety of pattern formation defects that are not necessarily expected. The ash2 gene is located in cytogenetic region 96A17–19 flanked by slowpoke and tolloid and is included in a cosmid that contains part of slowpoke. The ash2 transcript is 2.0 kb and is present throughout development. The ASH2 protein predicted from the nucleotide sequence of the open reading frame has a putative double zinc-finger domain, called a PHD finger, that is present not only in the products of other trithorax group genes such as TRX and MH1, but also in the product of a Polycomb group gene, PCL. Polyclonal antibodies directed against ASH2 detect the protein in imaginal discs and in the nuclei of salivary gland and fat body cells. On immunoblots these affinity-purified antibodies detect a 70-kDa protein in larvae and a 53-kDa protein in pupae.

scholarly journals Kinome-wide RNAi screen uncovers role of Ballchen in maintenance of gene activation by trithorax group in Drosophila

2020 ◽  
Author(s):  
Muhammad Haider Farooq Khan ◽  
Jawad Akhtar ◽  
Zain Umer ◽  
Najma Shaheen ◽  
Ammad Shaukat ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cell Fate ◽  
Target Genes ◽  
Genetic Interaction ◽  
Ex Vivo ◽  
Gene Activation ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Trithorax Group ◽  
Repressive Effect

AbstractPolycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG behaves as repressors to maintain heritable patterns of gene silencing and trxG act as anti-silencing factors by maintaining activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however the cellular signaling components that contribute to maintenance of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed to identify cell signaling genes that facilitate trxG to counteract PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase, known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibit strong genetic interaction with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL also affects expressions of trxG target genes in ball mutant embryos. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, analysis of genome-wide binding profile of BALL shows an overlap with 85% known binding sites of TRX across the genome. Both BALL and TRX are highly enriched at actively transcribed genes, which also correlate with presence of H3K4me3 and H3K27ac. We propose that BALL mediated signal positively contributes to the maintenance of gene activation by trxG by counteracting the repressive effect of PcG.

scholarly journals The Drosophila Polycomb Group Protein Psc Contacts ph and Pc through Specific Conserved Domains

1998 ◽  
Vol 18 (5) ◽  
pp. 2712-2720 ◽  
Author(s):  
Michael Kyba ◽  
Hugh W. Brock
Keyword(s):  
Amino Acids ◽  
Ring Finger ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Polycomb Group Protein ◽  
Yeast Two Hybrid System ◽  
Nuclear Extracts ◽  
Protein Binding Assay ◽  
Group Protein

ABSTRACT The Polycomb group proteins are transcriptional repressors that are thought to act through multimeric nuclear complexes. We show that ph and Psc coprecipitate with Pc from nuclear extracts. We have analyzed the domains required for the association of Psc with ph and Pc by using the yeast two-hybrid system and an in vitro protein-binding assay. Psc and ph interact through regions of sequence conservation with mammalian homologs, i.e., the H1 domain of ph (amino acids 1297 to 1418) and the helix-turn-helix-containing region of Psc (amino acids 336 to 473). Psc contacts Pc primarily at the helix-turn-helix-containing region of Psc (amino acids 336 to 473), but also at the ring finger (amino acids 250 to 335). The Pc chromobox is not required for this interaction. We discuss the implication of these results for the nature of the complexes formed by Polycomb group proteins.

scholarly journals Genome-wide RNAi screen in Drosophila reveals Enok as a novel trithorax group regulator

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Zain Umer ◽  
Jawad Akhtar ◽  
Muhammad Haider Farooq Khan ◽  
Najma Shaheen ◽  
Muhammad Abdul Haseeb ◽  
...  
Keyword(s):  
Hox Genes ◽  
Ex Vivo ◽  
Expression Patterns ◽  
Gene Activation ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Reporter System ◽  
Trithorax Group ◽  
Genome Wide ◽  
A Genome

Abstract Background Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the specialization of cell types by maintaining differential gene expression patterns. Initially discovered as positive regulators of HOX genes in forward genetic screens, trxG counteracts PcG-mediated repression of cell type-specific genes. Despite decades of extensive analysis, molecular understanding of trxG action and regulation are still punctuated by many unknowns. This study aimed at discovering novel factors that elicit an anti-silencing effect to facilitate trxG-mediated gene activation. Results We have developed a cell-based reporter system and performed a genome-wide RNAi screen to discover novel factors involved in trxG-mediated gene regulation in Drosophila. We identified more than 200 genes affecting the reporter in a manner similar to trxG genes. From the list of top candidates, we have characterized Enoki mushroom (Enok), a known histone acetyltransferase, as an important regulator of trxG in Drosophila. Mutants of enok strongly suppressed extra sex comb phenotype of Pc mutants and enhanced homeotic transformations associated with trx mutations. Enok colocalizes with both TRX and PC at chromatin. Moreover, depletion of Enok specifically resulted in an increased enrichment of PC and consequently silencing of trxG targets. This downregulation of trxG targets was also accompanied by a decreased occupancy of RNA-Pol-II in the gene body, correlating with an increased stalling at the transcription start sites of these genes. We propose that Enok facilitates trxG-mediated maintenance of gene activation by specifically counteracting PcG-mediated repression. Conclusion Our ex vivo approach led to identification of new trxG candidate genes that warrant further investigation. Presence of chromatin modifiers as well as known members of trxG and their interactors in the genome-wide RNAi screen validated our reverse genetics approach. Genetic and molecular characterization of Enok revealed a hitherto unknown interplay between Enok and PcG/trxG system. We conclude that histone acetylation by Enok positively impacts the maintenance of trxG-regulated gene activation by inhibiting PRC1-mediated transcriptional repression.

scholarly journals Kinome-Wide RNAi Screen Uncovers Role of Ballchen in Maintenance of Gene Activation by Trithorax Group in Drosophila

2021 ◽  
Vol 9 ◽  
Author(s):  
Muhammad Haider Farooq Khan ◽  
Jawad Akhtar ◽  
Zain Umer ◽  
Najma Shaheen ◽  
Ammad Shaukat ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Cell Fate ◽  
Target Genes ◽  
Ex Vivo ◽  
Gene Activation ◽  
Wide Distribution ◽  
Rnai Screen ◽  
Polycomb Group ◽  
Trithorax Group ◽  
Repressive Effect

Polycomb group (PcG) and trithorax group (trxG) proteins are evolutionary conserved factors that contribute to cell fate determination and maintenance of cellular identities during development of multicellular organisms. The PcG maintains heritable patterns of gene silencing while trxG acts as anti-silencing factors by conserving activation of cell type specific genes. Genetic and molecular analysis has revealed extensive details about how different PcG and trxG complexes antagonize each other to maintain cell fates, however, the cellular signaling components that contribute to the preservation of gene expression by PcG/trxG remain elusive. Here, we report an ex vivo kinome-wide RNAi screen in Drosophila aimed at identifying cell signaling genes that facilitate trxG in counteracting PcG mediated repression. From the list of trxG candidates, Ballchen (BALL), a histone kinase known to phosphorylate histone H2A at threonine 119 (H2AT119p), was characterized as a trxG regulator. The ball mutant exhibits strong genetic interactions with Polycomb (Pc) and trithorax (trx) mutants and loss of BALL affects expression of trxG target genes. BALL co-localizes with Trithorax on chromatin and depletion of BALL results in increased H2AK118 ubiquitination, a histone mark central to PcG mediated gene silencing. Moreover, BALL was found to substantially associate with known TRX binding sites across the genome. Genome wide distribution of BALL also overlaps with H3K4me3 and H3K27ac at actively transcribed genes. We propose that BALL mediated signaling positively contributes to the maintenance of gene activation by trxG in counteracting the repressive effect of PcG.

Sign in / Sign up

Export Citation Format

Share Document