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Trithorax

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https://www.readbyqxmd.com/read/29158494/mrg15-stimulates-ash1-h3k36-methyltransferase-activity-and-facilitates-ash1-trithorax-group-protein-function-in-drosophila
#1
Chang Huang, Fu Yang, Zhuqiang Zhang, Jing Zhang, Gaihong Cai, Lin Li, Yong Zheng, She Chen, Rongwen Xi, Bing Zhu
Ash1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29127737/genomic-data-from-arthropods-reveal-high-conservation-but-divergent-evolutionary-pattern-of-polycomb-trithorax-group-genes-in-arthropods
#2
Feng Jiang, Qing Liu, Xiang Liu, Xian-Hui Wang, Le Kang
Epigenetic gene control is maintained by chromatin-associated Polycomb group (PcG) and Trithorax group (TrxG) genes, which act antagonistically via the interplay between PcG and TrxG regulation to generate silenced or permissive transcriptional states. In this study, we searched for PcG/TrxG genes in 180 arthropod genomes, covering all the sequenced arthropod genomes at the time of conducting this study, to perform a global investigation of PcG/TrxG genes in a phylogenetic frame. Results of ancestral state reconstruction analysis revealed that the ancestor of arthropod species has an almost complete repertoire of PcG/TrxG genes, and most of these genes were seldom lost above order level...
November 11, 2017: Insect Science
https://www.readbyqxmd.com/read/29070704/bivalent-complexes-of-prc1-with-orthologs-of-brd4-and-moz-morf-target-developmental-genes-in-drosophila
#3
Hyuckjoon Kang, Youngsook L Jung, Kyle A McElroy, Barry M Zee, Heather A Wallace, Jessica L Woolnough, Peter J Park, Mitzi I Kuroda
Regulatory decisions in Drosophila require Polycomb group (PcG) proteins to maintain the silent state and Trithorax group (TrxG) proteins to oppose silencing. Since PcG and TrxG are ubiquitous and lack apparent sequence specificity, a long-standing model is that targeting occurs via protein interactions; for instance, between repressors and PcG proteins. Instead, we found that Pc-repressive complex 1 (PRC1) purifies with coactivators Fs(1)h [female sterile (1) homeotic] and Enok/Br140 during embryogenesis. Fs(1)h is a TrxG member and the ortholog of BRD4, a bromodomain protein that binds to acetylated histones and is a key transcriptional coactivator in mammals...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29069077/functional-convergence-of-histone-methyltransferases-ehmt1-and-kmt2c-involved-in-intellectual-disability-and-autism-spectrum-disorder
#4
Tom S Koemans, Tjitske Kleefstra, Melissa C Chubak, Max H Stone, Margot R F Reijnders, Sonja de Munnik, Marjolein H Willemsen, Michaela Fenckova, Connie T R M Stumpel, Levinus A Bok, Margarita Sifuentes Saenz, Kyna A Byerly, Linda B Baughn, Alexander P A Stegmann, Rolph Pfundt, Huiqing Zhou, Hans van Bokhoven, Annette Schenck, Jamie M Kramer
Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone methyltransferase 1 (EHMT1), is characterized by intellectual disability (ID), autism spectrum disorder (ASD), characteristic facial dysmorphisms, and other variable clinical features. In addition to EHMT1 mutations, de novo variants were reported in four additional genes (MBD5, SMARCB1, NR1I3, and KMT2C), in single individuals with clinical characteristics overlapping Kleefstra syndrome. Here, we present a novel cohort of five patients with de novo loss of function mutations affecting the histone methyltransferase KMT2C...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28974674/insights-into-beta-cell-regeneration-for-diabetes-via-integration-of-molecular-landscapes-in-human-insulinomas
#5
Huan Wang, Aaron Bender, Peng Wang, Esra Karakose, William B Inabnet, Steven K Libutti, Andrew Arnold, Luca Lambertini, Micheal Stang, Herbert Chen, Yumi Kasai, Milind Mahajan, Yayoi Kinoshita, Gustavo Fernandez-Ranvier, Thomas C Becker, Karen K Takane, Laura A Walker, Shira Saul, Rong Chen, Donald K Scott, Jorge Ferrer, Yevgeniy Antipin, Michael Donovan, Andrew V Uzilov, Boris Reva, Eric E Schadt, Bojan Losic, Carmen Argmann, Andrew F Stewart
Although diabetes results in part from a deficiency of normal pancreatic beta cells, inducing human beta cells to regenerate is difficult. Reasoning that insulinomas hold the "genomic recipe" for beta cell expansion, we surveyed 38 human insulinomas to obtain insights into therapeutic pathways for beta cell regeneration. An integrative analysis of whole-exome and RNA-sequencing data was employed to extensively characterize the genomic and molecular landscape of insulinomas relative to normal beta cells. Here, we show at the pathway level that the majority of the insulinomas display mutations, copy number variants and/or dysregulation of epigenetic modifying genes, most prominently in the polycomb and trithorax families...
October 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28961992/capturing-environmental-plant-memories-in-dna-with-a-little-help-from-chromatin
#6
Diana Mihaela Buzas
Plants are eukaryotes living mostly immotile in harsh environments. On occasion, it is beneficial for their survival to maintain a transcriptional response to an environmental stress longer than the stress lasts (transcriptional memory) and even to reiterate such a response more quickly or more strongly when the same stress is re-encountered (priming memory). In eukaryotes, transcription takes place in the context of chromatin, the packaging material of DNA. Chromatin regulation is often invoked when it comes to environmental transcriptional and priming memory in plants, but rarely chromatin-based regulation can be accurately assigned to a given aspect of transcription in vivo...
August 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28938122/genome-regulation-by-polycomb-and-trithorax-70-years-and-counting
#7
REVIEW
Bernd Schuettengruber, Henri-Marc Bourbon, Luciano Di Croce, Giacomo Cavalli
Polycomb (PcG) and Trithorax (TrxG) group proteins are evolutionarily conserved chromatin-modifying factors originally identified as part of an epigenetic cellular memory system that maintains repressed or active gene expression states. Recently, they have been shown to globally control a plethora of cellular processes. This functional diversity is achieved by their ability to regulate chromatin at multiple levels, ranging from modifying local chromatin structure to orchestrating the three-dimensional organization of the genome...
September 21, 2017: Cell
https://www.readbyqxmd.com/read/28934594/noncoding-rnas-in-polycomb-and-trithorax-regulation-a-quantitative-perspective
#8
Leonie Ringrose
The question of how noncoding RNAs are involved in Polycomb group (PcG) and Trithorax group (TrxG) regulation has been on an extraordinary journey over the last three decades. Favored models have risen and fallen, and healthy debates have swept back and forth. The field has recently reached a critical mass of compelling data that throws light on several previously unresolved issues. The time is ripe for a fruitful combination of these findings with two other long-running avenues of research, namely the biochemical properties of the PcG/TrxG system and the application of theoretical mathematical models toward an understanding of the system's regulatory properties...
September 15, 2017: Annual Review of Genetics
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#9
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#10
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28801151/correlation-between-desiccation-stress-response-and-epigenetic-modifications-of-genes-in-drosophila-melanogaster-an-example-of-environment-epigenome-interaction
#11
Vineeta Sharma, Surbhi Kohli, Vani Brahmachari
Animals from different phyla including arthropods tolerate water stress to different extent. This tolerance is accompanied by biochemical changes which in turn are due to transcriptional alteration. The changes in transcription can be an indirect effect on some of the genes, ensuing from the effect of stress on the regulators of transcription including epigenetic regulators. Within this paradigm, we investigated the correlation between stress response and epigenetic modification underlying gene expression modulation during desiccation stress in Canton-S...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#12
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28659357/menin-controls-the-memory-th2-cell-function-by-maintaining-the-epigenetic-integrity-of-th2-cells
#13
Atsushi Onodera, Masahiro Kiuchi, Kota Kokubo, Miki Kato, Tomohiro Ogino, Shu Horiuchi, Urara Kanai, Kiyoshi Hirahara, Toshinori Nakayama
Posttranslational modifications of histones are well-established epigenetic modifications that play an important role in gene expression and regulation. These modifications are partly mediated by the Trithorax group (TrxG) complex, which regulates the induction or maintenance of gene transcription. We investigated the role of Menin, a component of the TrxG complex, in the acquisition and maintenance of Th2 cell identity using T cell-specific Menin-deficient mice. Our gene expression analysis revealed that Menin was involved in the maintenance of the high expression of the previously identified Th2-specific genes rather than the induction of these genes...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28658556/epigenetic-regulation-of-t-helper-cell-differentiation-memory-and-plasticity-in-allergic-asthma
#14
REVIEW
Damon J Tumes, Magdalene Papadopoulos, Yusuke Endo, Atsushi Onodera, Kiyoshi Hirahara, Toshinori Nakayama
An estimated 300 million people currently suffer from asthma, which causes approximately 250 000 deaths a year. Allergen-specific T-helper (Th) cells produce cytokines that induce many of the hallmark features of asthma including airways hyperreactivity, eosinophilic and neutrophilic inflammation, mucus hypersecretion, and airway remodeling. Cytokine-producing Th subsets including Th1 (IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17), Th22 (IL-22), and T regulatory (IL-10) cells have all been suggested to play a role in the development of asthma...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28619824/setd1b-encoding-a-histone-3-lysine-4-methyltransferase-is-a-maternal-effect-gene-required-for-the-oogenic-gene-expression-program
#15
David Brici, Qinyu Zhang, Susanne Reinhardt, Andreas Dahl, Hella Hartmann, Kerstin Schmidt, Neha Goveas, Jiahao Huang, Lenka Gahurova, Gavin Kelsey, Konstantinos Anastassiadis, A Francis Stewart, Andrea Kranz
Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility in mice. Oocyte-specific Gdf9-iCre conditional knockout (Setd1b(Gdf9) cKO) ovaries develop through all stages; however, follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle...
July 15, 2017: Development
https://www.readbyqxmd.com/read/28550207/atx3-atx4-and-atx5-encode-putative-h3k4-methyltransferases-and-are-critical-for-plant-development
#16
Li-Qun Chen, Jin-Hong Luo, Zhen-Hai Cui, Ming Xue, Li Wang, Xiao-Yu Zhang, Wojciech P Pawlowski, Yan He
Methylation of Lys residues in the tail of the H3 histone is a key regulator of chromatin state and gene expression, conferred by a large family of enzymes containing an evolutionarily conserved SET domain. One of the main types of SET domain proteins are those controlling H3K4 di- and trimethylation. The genome of Arabidopsis (Arabidopsis thaliana) encodes 12 such proteins, including five ARABIDOPSIS TRITHORAX (ATX) proteins and seven ATX-Related proteins. Here, we examined three until-now-unexplored ATX proteins, ATX3, ATX4, and ATX5...
July 2017: Plant Physiology
https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#17
Jean-Baptiste Micol, Alessandro Pastore, Daichi Inoue, Nicolas Duployez, Eunhee Kim, Stanley Chun-Wei Lee, Benjamin H Durham, Young Rock Chung, Hana Cho, Xiao Jing Zhang, Akihide Yoshimi, Andrei Krivtsov, Richard Koche, Eric Solary, Amit Sinha, Claude Preudhomme, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, little is known about its paralog ASXL2, which is frequently mutated in acute myeloid leukemia patients bearing the RUNX1-RUNX1T1 (AML1-ETO) fusion. Here we report that ASXL2 is required for normal haematopoiesis with distinct, non-overlapping effects from ASXL1 and acts as a haploinsufficient tumour suppressor...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28421446/pre-tre-elements-act-as-transcription-activators-in-drosophila-s2-cells
#18
D A Chetverina, A V Mikhailova, P G Georgiev, M M Erokhin
The Drosophila PRE/TRE elements are DNA targets for Polycomb and Trithorax group proteins, which control repression and activation of gene transcription, respectively. In this study, we show that, in transiently transfected Drosophila S2 cells, bxdPRE activates transcription driven from different promoters. Using CG32795 gene promoter, we demonstrate that other PRE/TRE elements-Fab7, en, eve, and CycB-also act as transcription activators in this model system.
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28383693/molecular-basis-for-the-methylation-specificity-of-atxr5-for-histone-h3
#19
Elisa Bergamin, Sabina Sarvan, Josée Malette, Mohammad S Eram, Sylvain Yeung, Vanessa Mongeon, Monika Joshi, Joseph S Brunzelle, Scott D Michaels, Alexandre Blais, Masoud Vedadi, Jean-François Couture
In plants, the histone H3.1 lysine 27 (H3K27) mono-methyltransferases ARABIDOPSIS TRITHORAX RELATED PROTEIN 5 and 6 (ATXR5/6) regulate heterochromatic DNA replication and genome stability. Our initial studies showed that ATXR5/6 discriminate between histone H3 variants and preferentially methylate K27 on H3.1. In this study, we report three regulatory mechanisms contributing to the specificity of ATXR5/6. First, we show that ATXR5 preferentially methylates the R/F-K*-S/C-G/A-P/C motif with striking preference for hydrophobic and aromatic residues in positions flanking this core of five amino acids...
June 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331962/sex-combs-reduced-scr-regulatory-region-of-drosophila-revisited
#20
Juan M Calvo-Martín, Montserrat Papaceit, Carmen Segarra
The Hox gene Sex combs reduced (Scr) is responsible for the differentiation of the labial and prothoracic segments in Drosophila. Scr is expressed in several specific tissues throughout embryonic development, following a complex path that must be coordinated by an equally complex regulatory region. Although some cis-regulatory modules (CRMs) have been identified in the Scr regulatory region (~75 kb), there has been no detailed and systematic study of the distinct regulatory elements present within this region...
August 2017: Molecular Genetics and Genomics: MGG
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