DOCSLIB.ORG

Gene Section Short Communication

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Section Short Communication Atlas of Genetics and Cytogenetics in Oncology and Haematology INI ST -CNRS OPEN ACCESS JOURNAL Gene Section Short Communication MED28 (mediator complex subunit 28) Ming-Fen Lee, Chun-Yin Huang Department of Nutrition and Health Sciences, Chang Jung Christian University, 396 Sec 1 Changrong Rd, Gueiren Dist, Tainan, Taiwan 71101, China (MFL), Department of Nutrition, China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40402, China (CYH) Published in Atlas Database: July 2012 Online updated version : http://AtlasGeneticsOncology.org/Genes/MED28ID50131ch4p15.html DOI: 10.4267/2042/48468 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2013 Atlas of Genetics and Cytogenetics in Oncology and Haematology MED28 was also identified as a merlin-interacting Identity protein by yeast two-hybrid screen (Wiederhold et al., Other names: 1500003D12Rik, EG1, magicin 2004), where merlin, the neurofibromatosis 2 (NF2) HGNC (Hugo): MED28 tumor suppressor protein, belongs to the ezrin-radixin- Location: 4p15.32 moesin (ERM) family members. Affinity-binding assays demonstrated that MED28 interacted with the DNA/RNA SH3 domains of Grb2 (Wiederhold et al., 2004). Accordingly, MED28 was also named as magicin, Note merlin and Grb2 interacting cytoskeletal protein MED28 mRNA is identical to AF317679, AF358829, (Wiederhold et al., 2004). and AF321617 with the respective size of ~1, ~1.3, and In addition, several Src family members, including Src, ~3.2 kb (Wiederhold et al., 2004). They vary in the Fyn, and Lck, are also MED28-associated partners (Lee untranslated region, but share the same protein product. et al., 2006; Lu et al., 2006). Therefore, MED28/magicin/EG-1 may function as an Protein adaptor/scaffold to relay cellular signaling (Lee et al., 2006). Description Furthermore, MED28 is also found in the nucleus The full-length MED28 protein consists of 178 amino where it is presumably involved in gene transcription as acids with a predicted molecular weight ~20 kDa part of the Mediator complex (Sato et al., 2004). It is (Wiederhold et al., 2004). MED28, an evolutionaly likely that MED28 shuttles between nucleus, conserved protein, was identified as an endothelial- cytoskeleton, and cytoplasm to convey its physiological derived gene, EG-1 (Liu et al., 2002). role. Figure 1. Diagram of pre-mRNA of MED28. The black bars are exons. Atlas Genet Cytogenet Oncol Haematol. 2013; 17(1) 28 MED28 (mediator complex subunit 28) Lee MF, Huang CY Figure 2. MED28 interacting proteins. Expression mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) in MCF7 cells (Huang et al., 2012). MED28 is expressed in multiple human tissues In addition, overexpression of MED28 resulted in the (Wiederhold et al., 2004), with high expression in liver, activation of c-Src (Lu et al., 2006) and MED28 can be placenta, and testis (Liu et al., 2002). phosphorylated at Y64 by Fyn, a Src family member MED28-interacting proteins: merlin, actin, Grb2 (Lee et al., 2006). These data indicate that MED28 may (Wiederhold et al., 2004), Fyn, Lck, Src (Lee et al., function as a regulator of cellular signal transduction 2006; Lu et al., 2006), Mediator subunits (Sato et al., pathways. 2004). Cell proliferation: Localisation Ectopic overexpression of MED28 resulted in enhanced Cytoskeleton, cytoplasm, and nucleus (Sato et al., cell growth in immortal human embryonic kidney 2004; Wiederhold et al., 2004). (HEK) 293 cells, and breast cancer cell lines, MCF7 and MDA-MB-231 (Lu et al., 2005). The HEK293 Function xenograft tumor growth was also stimulated in MED28 may be involved in the regulation of numerous MED28-overexpressing cells (Lu et al., 2005). biological processes, including transcriptional Smooth muscle cell differentiation: regulation, cytoskeletal organization, signal MED28 functions a repressor of smooth muscle cell transduction, cell proliferation, differentiation, (SMC) differentiation (Beyer et al., 2007). MED28- angiogenesis, and migration (Beyer et al., 2007; Huang specific knockdown resulted in up-regulation of several et al., 2012; Liu et al., 2002; Wiederhold et al., 2004; SMC-related genes and SMC phenotype, whereas Yoon et al., 2010; Zhang et al., 2004). ectopic expression of MED28 reversed the SMC Transcription regulation: morphology induced by MED28 knockdown (Beyer et The Mediator complex is a set of protein coactivators al., 2007). that bridges DNA-binding transcription factors to Angiogenesis: transcriptional activation of the RNA polymerase II MED28 expression was increased by two-fold in (pol II). MED28 was identified as a subunit of the human umbilical vein endothelial cells (HUVECs) mammalian Mediator complex by the multidimensional treated with either tumor conditioned media or specific protein identification technology (MudPIT) (Sato et al., angiogenic factors (Liu et al., 2002). This observation 2004). This identification indicates a role of MED28 in suggests a role of MED28 in angiogenesis. the regulation of gene transcription. Cell migration: Cytoskeletal organization: The role of MED28 in cell migration was demonstrated The implication of MED28 in cytoskeletal re- in both estrogen receptor (ER)-positive and negative organization was based on the observation that human breast cancer cell lines (Huang et al., 2012; Lee MED28, similar to merlin, co-localizes with the actin et al., 2011). cytoskeleton as determined by cofractionation, Ectopic expression of MED28 increased cell migration immunofluorescence and electron microscopy and invasion in MCF7 and MDA-MB-231 breast (Wiederhold et al., 2004). cancer cells (Huang et al., 2012; Lee et al., 2011). Signal transduction: Investigation of the underlying mechanisms revealed Ectopic expression of MED28 led to increased that MED28 activates epidermal growth factor (EGF)- phosphorylation of mitogen-activated protein kinases stimulated migration through induction of matrix (MAPK) (Lu et al., 2005). In contrast, MED28-specific metalloproteinase 9 (MMP9) in EGFR-overexpressing knockdown resulted in decreased expression of MDA-MB-231 cells (Lee et al., 2011). Atlas Genet Cytogenet Oncol Haematol. 2013; 17(1) 29 MED28 (mediator complex subunit 28) Lee MF, Huang CY Figure 3. Biological functions of MED28. In addition, MED28 can also regulate cell migration Prognosis through the mitogen-activated protein kinase kinase 1 The evidence supporting MED28 as a prognostic factor (MAP2K1; MEK1)-dependent MMP2 activation, is emerging. MED28 peptide was detectable in serum which is independent of EGF stimulation (Huang et al., and urine of a small set of breast cancer patients (Lu et 2012). These lines of evidence support the role of al., 2007). In addition, statistical analysis on the MED28 in cell migration, implying that MED28 might correlation between MED28 and survival time or time- be responsible for cancer metastasis. to-relapse indicates that MED28 is a significant Homology predictor of malignant breast cancer (Yoon et al., 2010). MED28 has significant homology to a mouse cDNA (94%), fish, and a fly cDNA (31%) (Liu et al., 2002; References Wiederhold et al., 2004). The mouse MED28 gene is located on chromosome 5 (45520229..45529284). Liu C, Zhang L, Shao ZM, Beatty P, Sartippour M, Lane TF, Barsky SH, Livingston E, Nguyen M. Identification of a novel endothelial-derived gene EG-1. Biochem Biophys Res Implicated in Commun. 2002 Jan 11;290(1):602-12 Various cancers Sato S, Tomomori-Sato C, Parmely TJ, Florens L, Zybailov B, Swanson SK, Banks CA, Jin J, Cai Y, Washburn MP, Conaway Note JW, Conaway RC. A set of consensus mammalian mediator MED28 expression is elevated in cancers including subunits identified by multidimensional protein identification breast, colorectal, and prostate cancers, suggesting a technology. Mol Cell. 2004 Jun 4;14(5):685-91 role of MED28 in malignant phenotype of epithelial- Wiederhold T, Lee MF, James M, Neujahr R, Smith N, Murthy derived cancers (Liu et al., 2002; Zhang et al., 2004). A, Hartwig J, Gusella JF, Ramesh V. Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor Further tissue microarray (TMA) analysis on a set of merlin and Grb2. Oncogene. 2004 Nov 18;23(54):8815-25 breast cancer population also showed elevated MED28 expression in the ductal carcinoma in situ (DCIS) and Zhang L, Maul RS, Rao J, Apple S, Seligson D, Sartippour M, Rubio R, Brooks MN. Expression pattern of the novel gene invasive ductal carcinoma lesions (Yoon et al., 2010). EG-1 in cancer. Clin Cancer Res. 2004 May 15;10(10):3504-8 Such elevated MED28 expression independently Lu M, Zhang L, Maul RS, Sartippour MR, Norris A, Whitelegge predicts poor survival (Yoon et al., 2010). These data J, Rao JY, Brooks MN. The novel gene EG-1 stimulates indicate that MED28 may be a potential therapeutic cellular proliferation. Cancer Res. 2005 Jul 15;65(14):6159-66 target in cancer intervention. Indeed, MED28 Lee MF, Beauchamp RL, Beyer KS, Gusella JF, Ramesh V. suppression via either siRNA lentivirus or polyclonal Magicin associates with the Src-family kinases and is antibody resulted in decreased growth of both MCF7 phosphorylated upon CD3 stimulation. Biochem Biophys Res and MDA-MB-231 cell lines and their corresponding Commun. 2006 Sep 29;348(3):826-31 xenograft tumors in mice (Lu et al., 2007). Lu M, Zhang L, Sartippour MR, Norris AJ, Brooks MN. EG-1 Furthermore, the in vitro application of phytochemical interacts with c-Src and activates its signaling pathway. Int J resveratrol potently inhibited EGF-stimulated cell Oncol. 2006 Oct;29(4):1013-8 migration via suppression of MED28 in MDA-MB-231 Beyer KS, Beauchamp RL, Lee MF, Gusella JF, Näär AM, breast cancer cells (Lee et al., 2011). Ramesh V. Mediator subunit MED28 (Magicin) is a repressor Atlas Genet Cytogenet Oncol Haematol. 2013; 17(1) 30 MED28 (mediator complex subunit 28) Lee MF, Huang CY of smooth muscle cell differentiation. J Biol Chem. 2007 Nov epidermal growth factor (EGF)-induced migration in MDA-MB- 2;282(44):32152-7 231 human breast cancer cells. J Agric Food Chem. 2011 Nov 9;59(21):11853-61 Lu M, Sartippour MR, Zhang L, Norris AJ, Brooks MN.
Load more

Recommended publications
  • Genome-Wide Association Study of Body Weight
    Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight Hawlader A. Al-Mamun, Paul Kwan, Samuel A. Clark, Mohammad H. Ferdosi, Ross Tellam, Cedric Gondro To cite this version: Hawlader A. Al-Mamun, Paul Kwan, Samuel A. Clark, Mohammad H. Ferdosi, Ross Tellam, et al.. Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight. Genetics Selection Evolution, 2015, 47 (1), pp.66. 10.1186/s12711-015-0142-4. hal-01341302 HAL Id: hal-01341302 https://hal.archives-ouvertes.fr/hal-01341302 Submitted on 4 Jul 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. et al. Genetics Selection Evolution Al-Mamun (2015) 47:66 Genetics DOI 10.1186/s12711-015-0142-4 Selection Evolution RESEARCH ARTICLE Open Access Genome-wide association study of body weight in Australian Merino sheep reveals an orthologous region on OAR6 to human and bovine genomic regions affecting height and weight Hawlader A. Al-Mamun1,2, Paul Kwan2, Samuel A.
    [Show full text]
  • Functional Diversification of the Nleg Effector Family in Enterohemorrhagic Escherichia Coli
    Functional diversification of the NleG effector family in enterohemorrhagic Escherichia coli Dylan Valleaua, Dustin J. Littleb, Dominika Borekc,d, Tatiana Skarinaa, Andrew T. Quailea, Rosa Di Leoa, Scott Houlistone,f, Alexander Lemake,f, Cheryl H. Arrowsmithe,f, Brian K. Coombesb, and Alexei Savchenkoa,g,1 aDepartment of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 3E5, Canada; bDepartment of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4K1, Canada; cDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390; dDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390; ePrincess Margaret Cancer Centre, University of Toronto, Toronto, ON M5G 2M9, Canada; fDepartment of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; and gDepartment of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB T2N 4N1, Canada Edited by Ralph R. Isberg, Howard Hughes Medical Institute and Tufts University School of Medicine, Boston, MA, and approved August 15, 2018 (receivedfor review November 6, 2017) The pathogenic strategy of Escherichia coli and many other gram- chains. Depending on the length and nature of the polyubiquitin negative pathogens relies on the translocation of a specific set of chain, it posttranslationally regulates the target protein’s locali- proteins, called effectors, into the eukaryotic host cell during in- zation, activation, or degradation. Ubiquitination is a multistep fection. These effectors act in concert to modulate host cell pro- process which begins with the ubiquitin-activating enzyme (E1) cesses in favor of the invading pathogen. Injected by the type III using ATP to “charge” ubiquitin, covalently binding the ubiquitin secretion system (T3SS), the effector arsenal of enterohemorrhagic C terminus by a thioester linkage.
    [Show full text]
  • Whole Genome Resequencing of Four Italian Sweet Pepper Landraces Provides Insights on Sequence Variation in Genes of Agronomic V
    www.nature.com/scientificreports OPEN Whole genome resequencing of four Italian sweet pepper landraces provides insights on sequence variation in genes of agronomic value Alberto Acquadro1, Lorenzo Barchi1 ✉ , Ezio Portis1, Mohamed Nourdine1, Cristiano Carli2, Simone Monge3, Danila Valentino1 & Sergio Lanteri1 Sweet pepper (Capsicum annuum L.) is a high value crop and one of the most widely grown vegetables belonging to the Solanaceae family. In addition to commercial varieties and F1 hybrids, a multitude of landraces are grown, whose genetic combination is the result of hundreds of years of random, environmental, and farmer selection. High genetic diversity exists in the landrace gene pool which however has scarcely been studied, thus bounding their cultivation. We re-sequenced four pepper inbred lines, within as many Italian landraces, which representative of as many fruit types: big sized blocky with sunken apex (‘Quadrato’) and protruding apex or heart shaped (‘Cuneo’), elongated (‘Corno’) and smaller sized sub-spherical (‘Tumaticot’). Each genomic sequence was obtained through Illumina platform at coverage ranging from 39 to 44×, and reconstructed at a chromosome scale. About 35.5k genes were predicted in each inbred line, of which 22,017 were shared among them and the reference genome (accession ‘CM334’). Distinctive variations in miRNAs, resistance gene analogues (RGAs) and susceptibility genes (S-genes) were detected. A detailed survey of the SNP/Indels occurring in genes afecting fruit size, shape and quality identifed the highest frequencies of variation in regulatory regions. Many structural variations were identifed as presence/absence variations (PAVs), notably in resistance gene analogues (RGAs) and in the capsanthin/capsorubin synthase (CCS) gene.
    [Show full text]
  • Original Article Valproic Acid Decreases the Nuclear Localization of MDT-28, the Nematode Orthologue of MED28
    Original Article Valproic Acid Decreases the Nuclear Localization of MDT-28, the Nematode Orthologue of MED28 (Mediator complex / valproic acid / nuclear localization / MDT-28 / MED28) M. KOSTROUCHOVÁ1,2,*, V. KOSTROUCHOVÁ1, P. YILMA1, A. BENDA3, V. MANDYS2, M. KOSTROUCHOVÁ1,‡ 1Biocev, First Faculty of Medicine, Charles University, Prague, Czech Republic 2Department of Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic 3Imaging Methods Core Facility, Biocev, Faculty of Science, Charles University, Prague, Czech Republic Abstract. Mediator is a multiprotein complex that tode orthologue of MED28, as a likely target of lysine connects regulation mediated by transcription fac- acetylation using bioinformatic prediction of post- tors with RNA polymerase II transcriptional machin- translational modifications. Lysine acetylation was ery and integrates signals from the cell regulatory experimentally confirmed using anti-acetyl lysine cascades with gene expression. One of the Mediator antibody on immunoprecipitated GFP::MDT-28 ex- subunits, Mediator complex subunit 28 (MED28), pressed in synchronized C. elegans. Valproic acid has a dual nuclear and cytoplasmic localization and (VPA), a known inhibitor of lysine deacetylases, en- function. In the nucleus, MED28 functions as part of hanced the lysine acetylation of GFP::MDT-28. At Mediator and in the cytoplasm, it interacts with cy- the subcellular level, VPA decreased the nuclear lo- toskeletal proteins and is part of the regulatory cas- calization of GFP::MDT-28 detected by fluorescence- cades including that of Grb2. MED28 thus has the lifetime imaging microscopy (FLIM). This indicates potential to bring cytoplasmic regulatory interac- that the nuclear pool of MDT-28 is regulated by a tions towards the centre of gene expression regula- mechanism sensitive to VPA and provides an indirect tion.
    [Show full text]
  • The Human Gene Connectome As a Map of Short Cuts for Morbid Allele Discovery
    The human gene connectome as a map of short cuts for morbid allele discovery Yuval Itana,1, Shen-Ying Zhanga,b, Guillaume Vogta,b, Avinash Abhyankara, Melina Hermana, Patrick Nitschkec, Dror Friedd, Lluis Quintana-Murcie, Laurent Abela,b, and Jean-Laurent Casanovaa,b,f aSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065; bLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris Descartes University, Institut National de la Santé et de la Recherche Médicale U980, Necker Medical School, 75015 Paris, France; cPlateforme Bioinformatique, Université Paris Descartes, 75116 Paris, France; dDepartment of Computer Science, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; eUnit of Human Evolutionary Genetics, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Institut Pasteur, F-75015 Paris, France; and fPediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, 75015 Paris, France Edited* by Bruce Beutler, University of Texas Southwestern Medical Center, Dallas, TX, and approved February 15, 2013 (received for review October 19, 2012) High-throughput genomic data reveal thousands of gene variants to detect a single mutated gene, with the other polymorphic genes per patient, and it is often difficult to determine which of these being of less interest. This goes some way to explaining why, variants underlies disease in a given individual. However, at the despite the abundance of NGS data, the discovery of disease- population level, there may be some degree of phenotypic homo- causing alleles from such data remains somewhat limited. geneity, with alterations of specific physiological pathways under- We developed the human gene connectome (HGC) to over- come this problem.
    [Show full text]
  • Towards Personalized Medicine in Psychiatry: Focus on Suicide
    TOWARDS PERSONALIZED MEDICINE IN PSYCHIATRY: FOCUS ON SUICIDE Daniel F. Levey Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Program of Medical Neuroscience, Indiana University April 2017 ii Accepted by the Graduate Faculty, Indiana University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Andrew J. Saykin, Psy. D. - Chair ___________________________ Alan F. Breier, M.D. Doctoral Committee Gerry S. Oxford, Ph.D. December 13, 2016 Anantha Shekhar, M.D., Ph.D. Alexander B. Niculescu III, M.D., Ph.D. iii Dedication This work is dedicated to all those who suffer, whether their pain is physical or psychological. iv Acknowledgements The work I have done over the last several years would not have been possible without the contributions of many people. I first need to thank my terrific mentor and PI, Dr. Alexander Niculescu. He has continuously given me advice and opportunities over the years even as he has suffered through my many mistakes, and I greatly appreciate his patience. The incredible passion he brings to his work every single day has been inspirational. It has been an at times painful but often exhilarating 5 years. I need to thank Helen Le-Niculescu for being a wonderful colleague and mentor. I learned a lot about organization and presentation working alongside her, and her tireless work ethic was an excellent example for a new graduate student. I had the pleasure of working with a number of great people over the years. Mikias Ayalew showed me the ropes of the lab and began my understanding of the power of algorithms.
    [Show full text]
  • The Mammalian Mediator Complex
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 579 (2005) 904–908 FEBS 29061 Minireview The mammalian Mediator complex Joan Weliky Conawaya,b,c,*, Laurence Florensa, Shigeo Satoa, Chieri Tomomori-Satoa, Tari J. Parmelya, Tingting Yaoa, Selene K. Swansona, Charles A.S. Banksa, Michael P. Washburna, Ronald C. Conawaya,b a Stowers Institute for Medical Research, Kansas City, MO 64110, USA b Department of Biochemistry and Molecular Biology, Kansas University Medical Center, Kansas City, KS 66160, USA c Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA Received 25 October 2004; accepted 2 November 2004 Available online 24 November 2004 Edited by Gunnar von Heijne and Anders Liljas expressed in eukaryotes from yeast to man, is composed of Abstract The multiprotein Mediator (Med) complex is an evo- lutionarily conserved transcriptional regulator that plays impor- more than twenty subunits and has been named Mediator tant roles in activation and repression of RNA polymerase II (Med) for its role in mediating transcriptional signals from transcription. Prior studies identified a set of more than twenty DNA binding transcription factors bound at upstream pro- distinct polypeptides that compose the Saccharomyces cerevisiae moter elements and enhancers to RNA polymerase II and Mediator. Here we discuss efforts to characterize the subunit the general initiation factors bound at the core promoter sur- composition and associated activities of the mammalian Med rounding the transcriptional start site. complex. Ó 2004 Federation of European Biochemical Societies. Published by Elsevier B.V.
    [Show full text]
  • Structure of the Mammalian Mediator
    bioRxiv preprint doi: https://doi.org/10.1101/2020.10.05.326918; this version posted October 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Structure of the Mammalian Mediator Haiyan Zhao1.#, Natalie Young1,#, Jens Kalchschmidt2,#, Jenna Lieberman2, Laila El Khattabi3, Rafael Casellas2,4 and Francisco J. Asturias1,* 1Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora CO 80045, USA 2Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA 3Institut Cochin Laboratoire de Cytogénétique Constitutionnelle Pré et Post Natale, 75014 Paris France 4Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA #,*These authors contributed equally to this work *Correspondence should be addressed to F.J.A. ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.05.326918; this version posted October 6, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The Mediator complex plays an essential and multi-faceted role in regulation of RNA polymerase II transcription in all eukaryotes. Structural analysis of yeast Mediator has provided an understanding of the conserved core of the complex and its interaction with RNA polymerase II but failed to reveal the structure of the Tail module that contains most subunits targeted by activators and repressors. Here we present a molecular model of mammalian (Mus musculus) Mediator, derived from a 4.0 Å resolution cryo-EM map of the complex.
    [Show full text]
  • Investigating Host Genes Involved In. HIY Control by a Novel Computational Method to Combine GWAS with Eqtl
    Investigating Host Genes Involved in. HIY Control by a Novel Computational Method to Combine GWAS with eQTL by Yi Song THESIS Submitted In partial satisfaction of me teqoitements for the degree of MASTER OF SCIENCE In Biological and Medical Informatics In the GRADUATE DIVISION Copyright (2012) by Yi Song ii Acknowledgement First and foremost, I would like to thank my advisor Professor Hao Li, without whom this thesis would not have been possible. I am very grateful that Professor Li lead me into the field of human genomics and gave me the opportunity to pursue this interesting study in his laboratory. Besides the wealth of knowledge and invaluable insights that he offered in every meeting we had, Professor Li is one of the most approachable faculties I have met. I truly appreciate his patient guidance and his enthusiastic supervision throughout my master’s career. I am sincerely thankful to Professor Patricia Babbitt, the Associate Director of the Biomedical Informatics program at UCSF. Over my two years at UCSF, she has always been there to offer her help when I was faced with difficulties. I would also like to thank both Professor Babbitt and Professor Nevan Krogan for investing their valuable time in evaluating my work. I take immense pleasure in thanking my co-workers Dr. Xin He and Christopher Fuller. It has been a true enjoyment to discuss science with Dr. He, whose enthusiasm is a great inspiration to me. I also appreciate his careful editing of my thesis. Christopher Fuller, a PhD candidate in the Biomedical Informatics program, has provided great help for me on technical problems.
    [Show full text]
  • Effect of Single Nucleotide Polymorphisms on Intramuscular Fat Content in Hungarian Simmental Cattle
    Open Access Asian-Australas J Anim Sci Vol. 31, No. 9:1415-1419 September 2018 https://doi.org/10.5713/ajas.17.0773 pISSN 1011-2367 eISSN 1976-5517 Effect of single nucleotide polymorphisms on intramuscular fat content in Hungarian Simmental cattle István Anton1, Balázs Húth2,3, Imre Füller3, László Rózsa1, Gabriella Holló2, and Attila Zsolnai1,2,* * Corresponding Author: Attila Zsolnai Objective: To estimate effect of single nucleotide polymorphisms on the intramuscular fat Tel: +36-23-319-133, Fax: +36-23-319-133(120), E-mail: [email protected] content (IMF) of Hungarian Simmental bulls. Methods: Genotypes were determined on high-density Illumina Bovine DNA Chip. After 1 NARIC-Research Institute for Animal Breeding slaughtering of animals, chemical percentage of intramuscular fat was determined from Nutrition and Meat Science, Gesztenyes u. 1., Herceghalom, 2053, Hungary longissimus dorsi muscle. A multi-locus mixed-model was applied for statistical analyses. 2 Department of Animal Husbandry and Management, Results: Analyses revealed four loci (rs43284251, rs109210955, rs41630030, and rs41642251) Institute of Animal Science, Faculty of Agricultural to be highly associated (–log10P>12) with IMF located on chromosome 1, 6, 13, and 17, res- and Environmental Sciences, University of Kaposvár, Kaposvár, Guba S. u. 40., 7400, Hungary pectively. The frequency of their minor alleles was 0.426, 0.221, 0.162, and 0.106. 3 Association of Hungarian Simmental Cattle Breeders, Conclusion: The loci above can be useful in selection programs and
    [Show full text]
  • Structure of Mammalian Mediator Complex Reveals Tail Module Architecture and Interaction with a Conserved Core
    ARTICLE https://doi.org/10.1038/s41467-021-21601-w OPEN Structure of mammalian Mediator complex reveals Tail module architecture and interaction with a conserved core Haiyan Zhao 1,5, Natalie Young1,5, Jens Kalchschmidt2,5, Jenna Lieberman2, Laila El Khattabi3, ✉ Rafael Casellas2,4 & Francisco J. Asturias1 1234567890():,; The Mediator complex plays an essential and multi-faceted role in regulation of RNA poly- merase II transcription in all eukaryotes. Structural analysis of yeast Mediator has provided an understanding of the conserved core of the complex and its interaction with RNA polymerase II but failed to reveal the structure of the Tail module that contains most subunits targeted by activators and repressors. Here we present a molecular model of mammalian (Mus musculus) Mediator, derived from a 4.0 Å resolution cryo-EM map of the complex. The mammalian Mediator structure reveals that the previously unresolved Tail module, which includes a number of metazoan specific subunits, interacts extensively with core Mediator and has the potential to influence its conformation and interactions. 1 Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical School, Aurora, CO, USA. 2 Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD, USA. 3 Institut Cochin Laboratoire de Cytogénétique Constitutionnelle Pré et Post Natale, Paris, France. 4 Center for Cancer ✉ Research, NCI, NIH, Bethesda, MD, USA. 5These authors contributed equally: Haiyan Zhao, Natalie Young, Jens Kalchschmidt. email: Francisco. [email protected]
    [Show full text]
  • Elevated MED28 Expression Predicts Poor Outcome in Women with Breast Cancer
    UCLA UCLA Previously Published Works Title Elevated MED28 expression predicts poor outcome in women with breast cancer Permalink https://escholarship.org/uc/item/2pw3410d Journal BMC Cancer, 10(1) ISSN 1471-2407 Authors Yoon, Nam K Maresh, Erin L Elshimali, Yahya et al. Publication Date 2010-06-28 DOI http://dx.doi.org/10.1186/1471-2407-10-335 Supplemental Material https://escholarship.org/uc/item/2pw3410d#supplemental Peer reviewed eScholarship.org Powered by the California Digital Library University of California Yoon et al. BMC Cancer 2010, 10:335 http://www.biomedcentral.com/1471-2407/10/335 RESEARCH ARTICLE Open Access ElevatedResearch article MED28 expression predicts poor outcome in women with breast cancer Nam K Yoon1, Erin L Maresh1, Yahya Elshimali1, Ai Li2, Steve Horvath2,3,4, David B Seligson1,4, David Chia1,4 and Lee Goodglick*1,4 Abstract Background: MED28 (also known as EG-1 and magicin) has been implicated in transcriptional control, signal regulation, and cell proliferation. MED28 has also been associated with tumor progression in in vitro and in vivo models. Here we examined the association of MED28 expression with human breast cancer progression. Methods: Expression of MED28 protein was determined on a population basis using a high-density tissue microarray consisting of 210 breast cancer patients. The association and validation of MED28 expression with histopathological subtypes, clinicopathological variables, and disease outcome was assessed. Results: MED28 protein expression levels were increased in ductal carcinoma in situ and invasive ductal carcinoma of the breast compared to non-malignant glandular and ductal epithelium. Moreover, MED28 was a predictor of disease outcome in both univariate and multivariate analyses with higher expression predicting a greater risk of disease-related death.
    [Show full text]