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https://www.readbyqxmd.com/read/27912316/th2-cells-in-health-and-disease
#1
Toshinori Nakayama, Kiyoshi Hirahara, Atsushi Onodera, Yusuke Endo, Hiroyuki Hosokawa, Kenta Shinoda, Damon J Tumes, Yoshitaka Okamoto
Helper T (Th) cell subsets direct immune responses by producing signature cytokines. Th2 cells produce IL-4, IL-5, and IL-13, which are important in humoral immunity and protection from helminth infection and are central to the pathogenesis of many allergic inflammatory diseases. Molecular analysis of Th2 cell differentiation and maintenance of function has led to recent discoveries that have refined our understanding of Th2 cell biology. Epigenetic regulation of Gata3 expression by chromatin remodeling complexes such as Polycomb and Trithorax is crucial for maintaining Th2 cell identity...
November 28, 2016: Annual Review of Immunology
https://www.readbyqxmd.com/read/27888797/tumorigenicity-of-ewing-sarcoma-is-critically-dependent-on-the-trithorax-proteins-mll1-and-menin
#2
Laurie K Svoboda, Natashay Bailey, Raelene A Van Noord, Melanie A Krook, Ashley Harris, Cassondra Cramer, Brooke Jasman, Rajiv M Patel, Dafydd Thomas, Dmitry Borkin, Tomasz Cierpicki, Jolanta Grembecka, Elizabeth R Lawlor
Developmental transcription programs are epigenetically regulated by the competing actions of polycomb and trithorax (TrxG) protein complexes, which repress and activate genes, respectively. Ewing sarcoma is a developmental tumor that is associated with widespread de-regulation of developmental transcription programs, including HOX programs. Posterior HOXD genes are abnormally over-expressed by Ewing sarcoma and HOXD13, in particular, contributes to the tumorigenic phenotype. In MLL1 fusion-driven leukemia, aberrant activation of HOXA genes is epigenetically mediated by the TrxG complex and HOXA gene expression and leukemogenesis are critically dependent on the protein-protein interaction between the TrxG proteins MLL1 and menin...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27859962/concise-review-geminin-a-tale-of-two-tails-dna-replication-and-transcriptional-epigenetic-regulation-in-stem-cells
#3
Alexandra L Patmanidi, Spyridon Champeris Tsaniras, Dimitris Karamitros, Christina Kyrousi, Zoi Lygerou, Stavros Taraviras
Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells...
November 11, 2016: Stem Cells
https://www.readbyqxmd.com/read/27834868/steric-clash-in-the-set-domain-of-histone-methyltransferase-nsd1-as-a-cause-of-sotos-syndrome-and-its-genetic-heterogeneity-in-a-brazilian-cohort
#4
Kyungsoo Ha, Priya Anand, Jennifer A Lee, Julie R Jones, Chong Ae Kim, Debora Romeo Bertola, Jonathan D J Labonne, Lawrence C Layman, Wolfgang Wenzel, Hyung-Goo Kim
Most histone methyltransferases (HMTase) harbor a predicted Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, an HMTase at 5q35.2-35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations...
November 9, 2016: Genes
https://www.readbyqxmd.com/read/27813696/chromatin-changes-in-smarcal1-deficiency-a-hypothesis-for-the-gene-expression-alterations-of-schimke-immuno-osseous-dysplasia
#5
Marie Morimoto, Kunho Choi, Cornelius F Boerkoel, Kyoung Sang Cho
Mutations in SMARCAL1, which encodes a DNA annealing helicase with roles in DNA replication fork restart, DNA repair, and gene expression modulation, cause Schimke immuno-osseous dysplasia (SIOD), an autosomal recessive disease characterized by skeletal dysplasia, renal disease, T-cell immunodeficiency, and arteriosclerosis. The clinical features of SIOD arise from pathological changes in gene expression; however, the underlying mechanism for these gene expression alterations remains unclear. We hypothesized that changes of the epigenome alter gene expression in SIOD...
November 4, 2016: Nucleus
https://www.readbyqxmd.com/read/27812132/the-human-mixed-lineage-leukemia-5-mll5-a-sequentially-and-structurally-divergent-set-domain-containing-protein-with-no-intrinsic-catalytic-activity
#6
Sarah Mas-Y-Mas, Marta Barbon, Catherine Teyssier, Hélène Déméné, João E Carvalho, Louise E Bird, Andrey Lebedev, Juliana Fattori, Michael Schubert, Christian Dumas, William Bourguet, Albane le Maire
Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate...
2016: PloS One
https://www.readbyqxmd.com/read/27761696/histone-methyltransferase-txr1-is-required-for-both-h3-and-h3-3-lysine-27-methylation-in-the-well-known-ciliated-protist-tetrahymena-thermophila
#7
Xiaolu Zhao, Yuanyuan Wang, Yurui Wang, Yifan Liu, Shan Gao
DNA replication elongation is tightly controlled by histone-modifying enzymes. Our previous studies showed that the histone methytransferase TXR1 (Tetrahymena Trithorax related protein 1) specifically catalyzes H3K27 monomethylation and affects DNA replication elongation in Tetrahymena thermophila. In this study, we investigated whether TXR1 has a substrate preference to the canonical H3 over the replacement variant H3.3. We demonstrated by histone mutagenesis that K27Q mutation in H3.3 further aggravated the replication stress phenotype of K27Q mutation in canonical H3, supporting H3...
October 17, 2016: Science China. Life Sciences
https://www.readbyqxmd.com/read/27725578/a-primer-for-epigenetics-of-hematological-malignancies
#8
Hideaki Nakajima
Epigenetic marks, such as histone modifications or DNA methylation, regulate tissue specific gene expression by affecting the structures and accessibility of chromatin or DNA. Epigenetics, the molecular mechanisms regulating the epigenome, would therefore be critically involved in development and cell differentiation versus proliferation. Histone modifications include methylation, acetylation, phosphorylation and ubiquitination of specific lysine, arginine or serine residues on histone tails, and each modification has its own specific effect on gene expressions...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27601353/identification-of-set-domain-containing-proteins-in-gossypium-raimondii-and-their-response-to-high-temperature-stress
#9
Yong Huang, Yijia Mo, Pengyun Chen, Xiaoling Yuan, Funing Meng, Shengwei Zhu, Zhi Liu
SET (Su(var), E(z), and Trithorax) domain-containing proteins play an important role in plant development and stress responses through modifying lysine methylation status of histone. Gossypium raimondii may be the putative contributor of the D-subgenome of economical crops allotetraploid G. hirsutum and G. barbadense and therefore can potentially provide resistance genes. In this study, we identified 52 SET domain-containing genes from G. raimondii genome. Based on conserved sequences, these genes are grouped into seven classes and are predicted to catalyze the methylation of different substrates: GrKMT1 for H3K9me, GrKMT2 and GrKMT7 for H3K4me, GrKMT3 for H3K36me, GrKMT6 for H3K27me, but GrRBCMT and GrS-ET for nonhistones substrate-specific methylation...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27598373/intestinal-epithelial-cell-intrinsic-deletion-of-setd7-identifies-role-for-developmental-pathways-in-immunity-to-helminth-infection
#10
Menno J Oudhoff, Frann Antignano, Alistair L Chenery, Kyle Burrows, Stephen A Redpath, Mitchell J Braam, Georgia Perona-Wright, Colby Zaph
The intestine is a common site for a variety of pathogenic infections. Helminth infections continue to be major causes of disease worldwide, and are a significant burden on health care systems. Lysine methyltransferases are part of a family of novel attractive targets for drug discovery. SETD7 is a member of the Suppressor of variegation 3-9-Enhancer of zeste-Trithorax (SET) domain-containing family of lysine methyltransferases, and has been shown to methylate and alter the function of a wide variety of proteins in vitro...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27581385/polycomb-and-trithorax-opposition-in-development-and-disease
#11
Steven T Poynter, Cigall Kadoch
Early discoveries in chromatin biology and epigenetics heralded new insights into organismal development. From these studies, two mediators of cellular differentiation were discovered: the Polycomb group (PcG) of transcriptional repressors, and the trithorax group (trxG) of transcriptional activators. These protein families, while opposed in function, work together to coordinate the appropriate cellular developmental programs that allow for both embryonic stem cell self-renewal and differentiation. Recently, both the PcG and trxG chromatin modulators have been observed to be deregulated in a wide spectrum diseases including developmental disorders and cancer...
November 2016: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/27527698/the-role-of-additional-sex-combs-like-proteins-in-cancer
#12
Jean-Baptiste Micol, Omar Abdel-Wahab
Additional sex combs-like (ASXL) proteins are mammalian homologs of Addition of sex combs (Asx), a protein that regulates the balance of trithorax and Polycomb function in Drosophila. All three ASXL family members (ASXL1, ASXL2, and ASXL3) are affected by somatic or de novo germline mutations in cancer or rare developmental syndromes, respectively. Although Asx is characterized as a catalytic partner for the deubiquitinase Calypso (or BAP1), there are domains of ASXL proteins that are distinct from Asx and the roles and redundancies of ASXL members are not yet well understood...
October 3, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27510973/control-of-germline-stem-cell-differentiation-by-polycomb-and-trithorax-group-genes-in-the-niche-microenvironment
#13
Xuewen Li, Fu Yang, Hongyan Chen, Bowen Deng, Xinghua Li, Rongwen Xi
Polycomb and Trithorax group (PcG and TrxG) genes function to regulate gene transcription by maintaining a repressive or active chromatin state, respectively. This antagonistic activity is important for body patterning during embryonic development, but whether this function module has a role in adult tissues is unclear. Here, we report that in the Drosophila ovary, disruption of the Polycomb repressive complex 1 (PRC1), specifically in the supporting escort cells, causes blockage of cystoblast differentiation and germline stem cell-like tumor formation...
October 1, 2016: Development
https://www.readbyqxmd.com/read/27508387/phenotypic-plasticity-through-transcriptional-regulation-of-the-evolutionary-hotspot-gene-tan-in-drosophila-melanogaster
#14
Jean-Michel Gibert, Emmanuèle Mouchel-Vielh, Sandra De Castro, Frédérique Peronnet
Phenotypic plasticity is the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions. Phenotypic plasticity can be adaptive. Furthermore, it is thought to facilitate evolution. Although phenotypic plasticity is a widespread phenomenon, its molecular mechanisms are only beginning to be unravelled. Environmental conditions can affect gene expression through modification of chromatin structure, mainly via histone modifications, nucleosome remodelling or DNA methylation, suggesting that phenotypic plasticity might partly be due to chromatin plasticity...
August 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27447986/an-evolutionary-conserved-epigenetic-mark-of-polycomb-response-elements-implemented-by-trx-mll-compass
#15
Ryan Rickels, Deqing Hu, Clayton K Collings, Ashley R Woodfin, Andrea Piunti, Man Mohan, Hans-Martin Herz, Evgeny Kvon, Ali Shilatifard
Polycomb response elements (PREs) are specific DNA sequences that stably maintain the developmental pattern of gene expression. Drosophila PREs are well characterized, whereas the existence of PREs in mammals remains debated. Accumulating evidence supports a model in which CpG islands recruit Polycomb group (PcG) complexes; however, which subset of CGIs is selected to serve as PREs is unclear. Trithorax (Trx) positively regulates gene expression in Drosophila and co-occupies PREs to antagonize Polycomb-dependent silencing...
July 21, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27446595/role-of-transcriptional-read-through-in-pre-activity-in-drosophila-melanogaster
#16
P V Elizar'ev, D V Lomaev, D A Chetverina, P G Georgiev, M M Erokhin
Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4...
April 2016: Acta Naturae
https://www.readbyqxmd.com/read/27434206/ash1l-a-histone-methyltransferase-protein-is-a-novel-candidate-globin-gene-regulator-revealed-by-genetic-study-of-an-english-family-with-beta-thalassaemia-unlinked-to-the-beta-globin-locus
#17
Amandine Breton, Andria Theodorou, Suleyman Aktuna, Laura Sonzogni, David Darling, Lucas Chan, Stephan Menzel, Peter J van der Spek, Sigrid M A Swagemakers, Frank Grosveld, Sjaak Philipsen, Swee Lay Thein
In 1993, we described an English family with beta-thalassaemia that was not linked to the beta-globin locus. Whole genome sequence analyses revealed potential causative mutations in 15 different genes, of which 4 were consistently and uniquely associated with the phenotype in all 7 affected family members, also confirmed by genetic linkage analysis. Of the 4 genes, which are present in a centromeric region of chromosome 1, ASH1L was proposed as causative through functional mRNA knock-down and chromatin-immunoprecipitation studies in human erythroid progenitor cells...
July 19, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27428271/interaction-of-the-chromatin-remodeling-protein-hino80-with-dna
#18
Shweta Mendiratta, Shipra Bhatia, Shruti Jain, Taniya Kaur, Vani Brahmachari
The presence of a highly conserved DNA binding domain in INO80 subfamily predicted that INO80 directly interacts with DNA and we demonstrated its DNA binding activity in vitro. Here we report the consensus motif recognized by the DBINO domain identified by SELEX method and demonstrate the specific interaction of INO80 with the consensus motif. We show that INO80 significantly down regulates the reporter gene expression through its binding motif, and the repression is dependent on the presence of INO80 but not YY1 in the cell...
2016: PloS One
https://www.readbyqxmd.com/read/27401231/lolal-is-an-evolutionarily-new-epigenetic-regulator-of-dpp-transcription-during-dorsal-ventral-axis-formation
#19
Janine C Quijano, Robert G Wisotzkey, Nancy Lan Tran, Yunxian Huang, Michael J Stinchfield, Theodor E Haerry, Osamu Shimmi, Stuart J Newfeld
Secreted ligands in the Dpp/BMP family drive dorsal-ventral (D/V) axis formation in all Bilaterian species. However, maternal factors regulating Dpp/BMP transcription in this process are largely unknown. We identified the BTB domain protein longitudinals lacking-like (lolal) as a modifier of decapentaplegic (dpp) mutations. We show that Lolal is evolutionarily related to the Trithorax group of chromatin regulators and that lolal interacts genetically with the epigenetic factor Trithorax-like during Dpp D/V signaling...
October 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27317809/functional-analysis-of-aebp2-a-prc2-polycomb-protein-reveals-a-trithorax-phenotype-in-embryonic-development-and-in-escs
#20
Anne Grijzenhout, Jonathan Godwin, Haruhiko Koseki, Michal Ryszard Gdula, Dorota Szumska, Joanna F McGouran, Shoumo Bhattacharya, Benedikt M Kessler, Neil Brockdorff, Sarah Cooper
The Polycomb repressive complexes PRC1 and PRC2 are key mediators of heritable gene silencing in multicellular organisms. Here, we characterise AEBP2, a known PRC2 co-factor which, in vitro, has been shown to stimulate PRC2 activity. We show that AEBP2 localises specifically to PRC2 target loci, including the inactive X chromosome. Proteomic analysis confirms that AEBP2 associates exclusively with PRC2 complexes. However, analysis of embryos homozygous for a targeted mutation of Aebp2 unexpectedly revealed a Trithorax phenotype, normally linked to antagonism of Polycomb function...
August 1, 2016: Development
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