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Trithorax

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https://www.readbyqxmd.com/read/28516957/asxl2-is-essential-for-haematopoiesis-and-acts-as-a-haploinsufficient-tumour-suppressor-in-leukemia
#1
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
#2
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
#3
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...
April 5, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28331962/sex-combs-reduced-scr-regulatory-region-of-drosophila-revisited
#4
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...
March 22, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28327288/atrophin-controls-developmental-signaling-pathways-via-interactions-with-trithorax-like
#5
Kelvin Yeung, Ann Boija, Edvin Karlsson, Per-Henrik Holmqvist, Yonit Tsatskis, Ilaria Nisoli, Damian Yap, Alireza Lorzadeh, Michelle Moksa, Martin Hirst, Samuel Aparicio, Manolis Fanto, Per Stenberg, Mattias Mannervik, Helen McNeill
Mutations in human Atrophin1, a transcriptional corepressor, cause dentatorubral-pallidoluysian atrophy, a neurodegenerative disease. Drosophila Atrophin (Atro) mutants display many phenotypes, including neurodegeneration, segmentation, patterning and planar polarity defects. Despite Atro's critical role in development and disease, relatively little is known about Atro's binding partners and downstream targets. We present the first genomic analysis of Atro using ChIP-seq against endogenous Atro. ChIP-seq identified 1300 potential direct targets of Atro including engrailed, and components of the Dpp and Notch signaling pathways...
March 22, 2017: ELife
https://www.readbyqxmd.com/read/28228601/loss-of-tumor-suppressor-kdm6a-amplifies-prc2-regulated-transcriptional-repression-in-bladder-cancer-and-can-be-targeted-through-inhibition-of-ezh2
#6
Lian Dee Ler, Sujoy Ghosh, Xiaoran Chai, Aye Aye Thike, Hong Lee Heng, Ee Yan Siew, Sucharita Dey, Liang Kai Koh, Jing Quan Lim, Weng Khong Lim, Swe Swe Myint, Jia Liang Loh, Pauline Ong, Xin Xiu Sam, Dachuan Huang, Tony Lim, Puay Hoon Tan, Sanjanaa Nagarajan, Christopher Wai Sam Cheng, Henry Ho, Lay Guat Ng, John Yuen, Po-Hung Lin, Cheng-Keng Chuang, Ying-Hsu Chang, Wen-Hui Weng, Steven G Rozen, Patrick Tan, Caretha L Creasy, See-Tong Pang, Michael T McCabe, Song Ling Poon, Bin Tean Teh
Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder carcinoma, KDM6A (a H3K27 demethylase) is frequently mutated, but its functional consequences and therapeutic targetability remain unknown. About 70% of KDM6A mutations resulted in a total loss of expression and a consequent loss of demethylase function in this cancer type...
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28193136/ccctc-binding-factor-transcriptionally-targets-wdr5-to-mediate-somatic-cell-reprogramming
#7
Feng Wang, Jinghua Han, Li Wang, Ying Jing, Zhu Zhu, Dawei Hui, Zhaohui Wang, Yangzi Wang, Yang Dong, Tao Tan
It was previously reported that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax complex, is a key regulator for the maintenance of embryonic stem (ES) cell pluripotency and somatic cell reprogramming. However, it remains unclear whether other factors are also involved in this process. Here, we show that CTCF is an upstream regulator of Wdr5: It physically associates with Wdr5 and further transcriptionally controls its expression by directly targeting the Wdr5 gene promoter. As a downstream effector, overexpression of Wdr5 can rescue ES cells from growth defects and decreased formation of induced pluripotent stem cells caused by CTCF knockdown...
May 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28188343/mll5-kmt2e-structure-function-and-clinical-relevance
#8
REVIEW
Xiaoming Zhang, Wisna Novera, Yan Zhang, Lih-Wen Deng
The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A-2D and 2F-2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28185526/low-expression-of-ash2l-protein-correlates-with-a-favorable-outcome-in-acute-myeloid-leukemia
#9
Jill S Butler, Yi Hua Qiu, Nianxiang Zhang, Suk-Young Yoo, Kevin R Coombes, Sharon Y R Dent, Steven M Kornblau
ASH2L encodes a trithorax group protein that is a core component of all characterized mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes. ASH2L protein levels in primary leukemia patient samples have not yet been defined. We analyzed ASH2L protein expression in 511 primary AML patient samples using reverse phase protein array (RPPA) technology. We discovered that ASH2L expression is significantly increased in a subset of patients carrying fms-related tyrosine kinase 3 (FLT3) mutations...
May 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28097693/distinguishing-between-biochemical-and-cellular-function-are-there-peptide-signatures-for-cellular-function-of-proteins
#10
Shruti Jain, Kausik Bhattacharyya, Rachit Bakshi, Ankita Narang, Vani Brahmachari
The genome annotation and identification of gene function depends on conserved biochemical activity. However, in the cell, proteins with the same biochemical function can participate in different cellular pathways and cannot complement one another. Similarly, two proteins of very different biochemical functions are put in the same class of cellular function; for example, the classification of a gene as an oncogene or a tumour suppressor gene is not related to its biochemical function, but is related to its cellular function...
January 18, 2017: Proteins
https://www.readbyqxmd.com/read/28058687/the-reasons-of-trithorax-like-expression-disturbance-in-trl-3609-allele-of-drosophila-melanogaster
#11
D A Karagodin, N V Battulina, T I Merkulova, E M Baricheva
The regulatory region of the Trl gene was analyzed using the mutation Trl (3609) , resulting from the insertion of the P-element into the promoter region of the gene as well as mutations obtained on its basis. It is shown that two last transcription start sites, which are most often used in vitro in S2 cells, are almost not used in vivo. Experimental data indicate that transcription terminators in transposons play an important role in the decrease in the transcription level of the recipient gene.
November 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28044469/epigenetic-silencing-and-activation-of-transcription-influence-on-the-radiation-sensitivity-of-glioma-cell-lines
#12
Ali Sak, Dennis Kübler, Kristina Bannik, Michael Groneberg, Sonja Strunz, Ralf Kriehuber, Martin Stuschke
PURPOSE: To uncover the role of EZH2 and its opponent ASHL2, a polycomb and trithorax group protein, respectively, on the radioresponsiveness of glioma cell lines. MATERIALS AND METHODS: Expression of EZH2 and ASHL2 was inhibited by siRNA in glioma cell lines. The effect on histone methylation, gene expression, DNA damage repair signaling, cell cycle checkpoints, apoptosis and tumor control were evaluated. RESULTS: Inhibition of EZH2 (EZH2i) led to a transcriptional dysregulation with upregulation of 544 and downregulation of 445 genes...
May 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28028228/large-scale-heterochromatin-remodeling-linked-to-overreplication-associated-dna-damage
#13
Wei Feng, Christopher J Hale, Ryan S Over, Shawn J Cokus, Steven E Jacobsen, Scott D Michaels
Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX-RELATED 5 (ATXR5) and ATXR6 (ATXR6) results in the overreplication of heterochromatin. Here we show that the overreplication results in DNA damage and extensive chromocenter remodeling into unique structures we have named "overreplication-associated centers" (RACs). RACs have a highly ordered structure with an outer layer of condensed heterochromatin, an inner layer enriched in the histone variant H2AX, and a low-density core containing foci of phosphorylated H2AX (a marker of double-strand breaks) and the DNA-repair enzyme RAD51...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27941795/smarca4-atpase-mutations-disrupt-direct-eviction-of-prc1-from-chromatin
#14
Benjamin Z Stanton, Courtney Hodges, Joseph P Calarco, Simon M G Braun, Wai Lim Ku, Cigall Kadoch, Keji Zhao, Gerald R Crabtree
Trithorax-group proteins and their mammalian homologs, including those in BAF (mSWI/SNF) complexes, are known to oppose the activity of Polycomb repressive complexes (PRCs). This opposition underlies the tumor-suppressive role of BAF subunits and is expected to contribute to neurodevelopmental disorders. However, the mechanisms underlying opposition to Polycomb silencing are poorly understood. Here we report that recurrent disease-associated mutations in BAF subunits induce genome-wide increases in PRC deposition and activity...
February 2017: Nature Genetics
https://www.readbyqxmd.com/read/27935206/developmental-transcriptional-regulation-by-sumoylation-an-evolving-field
#15
REVIEW
Juan Monribot-Villanueva, Mario Zurita, Martha Vázquez
SUMOylation is a reversible post-translational protein modification that affects the intracellular localization, stability, activity, and interactions of its protein targets. The SUMOylation pathway influences several nuclear and cytoplasmic processes. The expression of many genes, in particular those involved in development is finely tuned in space and time by several groups of proteins. There is growing evidence that transcriptional regulation mechanisms involve direct SUMOylation of transcriptional-related proteins such as initiation and elongation factors, and subunits of chromatin modifier and remodeling complexes originally described as members of the trithorax and Polycomb groups in Drosophila...
March 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/27932267/human-pre-pik3c2b-an-intronic-cis-element-with-dual-function-of-activation-and-repression
#16
Jayant Maini, Mohsen Ghasemi, Deepti Yandhuri, Suman S Thakur, Vani Brahmachari
The Polycomb/Trithorax Responsive Elements (PRE/TREs) are the cis-regulatory sequences that interact with both repressive (PcG) as well as activating (TrxG) complexes. However, most of the mammalian PREs are demonstrated to interact with the repressive polycomb (PcG) complexes only. We have carried out an unbiased search for proteins interacting with human PRE-PIK3C2B (hPRE-PIK3C2B) based on DNA affinity purification followed by mass spectrometry and identified MLL, MLL4 and WDR87 among other proteins in three biological replicates in HEK, U87 and HeLa cell lines...
December 6, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27924120/hippophae-rhamnoides-n-glycoproteome-analysis-a-small-step-towards-sea-buckthorn-proteome-mining
#17
Yaiphabi Sougrakpam, Renu Deswal
Hippophae rhamnoides is a hardy shrub capable of growing under extreme environmental conditions namely, high salt, drought and cold. Its ability to grow under extreme conditions and its wide application in pharmaceutical and nutraceutical industry calls for its in-depth analysis. N-glycoproteome mining by con A affinity chromatography from seedling was attempted. The glycoproteome was resolved on first and second dimension gel electrophoresis. A total of 48 spots were detected and 10 non-redundant proteins were identified by MALDI-TOF/TOF...
October 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
https://www.readbyqxmd.com/read/27912316/th2-cells-in-health-and-disease
#18
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
#19
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...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27859962/concise-review-geminin-a-tale-of-two-tails-dna-replication-and-transcriptional-epigenetic-regulation-in-stem-cells
#20
REVIEW
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...
February 2017: Stem Cells
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