Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases
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Additional Methods
Additional Methods Cell Expression Profiles The tissue-dependent gene expression dataset from the Genome Novartis Foundation contains 32 healthy major tissues, and 47 tumour samples and cell lines. The custom- designed whole-genome gene expression microarrays used on each sample targets 44775 human mRNA transcripts. Previous analysis of this dataset identified many chromo- somal regions of correlated transcription that are under the control of both tissue and parental allele-specific expression. The expression levels of TF genes across tissue sam- ples are observed to be lower than non-TF genes. This is coherent with the mechanistic explanation that the effect of a single TF molecule is amplified by transcribing many copies of mRNA from a target gene. Across all samples, the proportion of TFs rel- ative to all expressed genes is remarkably stable at ∼ 6%. In the bootstrap test for highly predictive CRMs, we resampled from this set of TFs to generate the bootstrap replicates. High variance in gene expression profiles are observed between replicates for samples with more heterogeneous composition. Therefore, we treat each replicate as an independent sample in our analysis. When analyzing expression variation in a single sample, we found that a Gaussian distributional assumption for gene expression is more suitable compared to other distributions. Smoothing and Model Fitting Since gene expression response by the target gene varies over different TF expression values in a smooth fashion, a curved function is needed to fit our gene expression data. For additive models, the partial response of the target gene to the expression of each TF is described by a smooth function. -
Alpha Actinin 4: an Intergral Component of Transcriptional
ALPHA ACTININ 4: AN INTERGRAL COMPONENT OF TRANSCRIPTIONAL PROGRAM REGULATED BY NUCLEAR HORMONE RECEPTORS By SIMRAN KHURANA Submitted in partial fulfillment of the requirements for the degree of doctor of philosophy Thesis Advisor: Dr. Hung-Ying Kao Department of Biochemistry CASE WESTERN RESERVE UNIVERSITY August, 2011 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of SIMRAN KHURANA ______________________________________________________ PhD candidate for the ________________________________degree *. Dr. David Samols (signed)_______________________________________________ (chair of the committee) Dr. Hung-Ying Kao ________________________________________________ Dr. Edward Stavnezer ________________________________________________ Dr. Leslie Bruggeman ________________________________________________ Dr. Colleen Croniger ________________________________________________ ________________________________________________ May 2011 (date) _______________________ *We also certify that written approval has been obtained for any proprietary material contained therein. TABLE OF CONTENTS LIST OF TABLES vii LIST OF FIGURES viii ACKNOWLEDEMENTS xii LIST OF ABBREVIATIONS xiii ABSTRACT 1 CHAPTER 1: INTRODUCTION Family of Nuclear Receptors 3 Mechanism of transcriptional regulation by co-repressors and co-activators 8 Importance of LXXLL motif of co-activators in NR mediated transcription 12 Cyclic recruitment of co-regulators on the target promoters 15 Actin and actin related proteins (ABPs) in transcription -
Mouse Anti-Human Testicular Receptor 4
Catalog Clonality, clone Reactive Reg. Product Name Quantity Applications Number (isotype) species Status mAb clone H0107B WB, ELISA, 434700 Mouse anti-human TR4 100 µg Hu, Ms, Rt RUO (Ms IgG2a) IP, IHC Mouse Anti-Human Testicular Receptor 4 Description Testicular receptor 4 (TR4, TAK1; NR2C2) is a member of the orphan nuclear receptor family. TR4 was originally cloned from lymphoblastoma Raji cells or mouse brain cDNA library. No ligand has been reported. Northern blot shows TR4 is transcribed as a 9kb mRNA in many tissues and as a 2.8kb mRNA in testis, mainly in spermatocytes. TR4 has two isoforms called TR4α1 and TR4-α2, which differ in 19 amino acids coded by two separate exons. Both products translated from 9kb transcript are ubiquitously expressed. Since TR4 binds to the same elements for the RAR-RXR or TR-RXR heterodimers, TR4 may have an inhibitory affect for retinoic-acid mediated transactivation. Nomenclature NR2C2 Genbank L27586 Origin Produced in BALB/c mouse ascites after inoculation with hybridoma of mouse myeloma cells (NS-1) and spleen cells derived from a BALB/c mouse immunized with Baculovirus-expressed recombinant human TR4 (23-52 aa). Specificity This antibody specifically recognizes human TR4 and cross reacts with mouse and rat TR4. Purification Ammonium sulfate fractionation Formulation Concentration is 1 mg/mL in physiological saline with 0.1% sodium azide as a preservative. Application Recommended Concentration* Western Blot 2 μg/mL Non reducing Western Blot Not tested ELISA 0.1 μg/mL Immunoprecipitation Determine by use Electrophoretic Mobility Shift Assay Not tested Chromatin Immunoprecipitation Not tested Immunohistochemistry 10 μg/mL *In order to obtain the best results, optimal working dilutions should be determined by each individual user. -
Multiple Functions and Essential Roles of Nuclear Receptor Coactivators of Bhlh-PAS Family
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ENDOCRINE REGULATIONS, Vol. 50, No. 3, 165–181, 2016 165 doi:10.1515/enr-2016-0019 Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family Pecenova L, Farkas R Laboratory of Developmental Genetics, Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia E-mail: [email protected] Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numer- ous metabolic pathways, and can be misregulated in many types of cancers. Their enormous func- tional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and high- light some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways. -
Identifying the Role of Wilms Tumor 1 Associated Protein in Cancer Prediction Using Integrative Genomic Analyses
MOLECULAR MEDICINE REPORTS 14: 2823-2831, 2016 Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses LI‑SHENG WU1*, JIA-YI QIAN2*, MINGHAI WANG3* and HAIWEI YANG4 1Department of General Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001; 2Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029; 3Department of General Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002; 4Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China Received August 31, 2015; Accepted June 2, 2016 DOI: 10.3892/mmr.2016.5528 Abstract. The Wilms tumor suppressor, WT1 was first iden- regulatory factor 1, glucocorticoid receptor and peroxisome tified due to its essential role in the normal development of proliferator‑activated receptor γ transcription factor binding the human genitourinary system. Wilms tumor 1 associated sites were identified in the upstream (promoter) region of the protein (WTAP) was subsequently revealed to interact with human WTAP gene, suggesting that these transcription factors WT1 using yeast two‑hybrid screening. The present study may be involved in WTAP functions in tumor formation. identified 44 complete WTAP genes in the genomes of verte- brates, including fish, amphibians, birds and mammals. The Introduction vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From The Wilms tumor suppressor gene WT1 was first identified 1,347 available SNPs in the human WTAP gene, 19 were due to its essential role in the normal development of the identified to cause missense mutations. -
Full-Text PDF (Final Published Version)
Alexander, S. P. H., Cidlowski, J. A., Kelly, E., Marrion, N. V., Peters, J. A., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators (2017). THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors. British Journal of Pharmacology, 174, S208-S224. https://doi.org/10.1111/bph.13880 Publisher's PDF, also known as Version of record License (if available): CC BY Link to published version (if available): 10.1111/bph.13880 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Wiley at https://doi.org/10.1111/bph.13880 . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2017/18: Nuclear hormone receptors. British Journal of Pharmacology (2017) 174, S208–S224 THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors Stephen PH Alexander1, John A Cidlowski2, Eamonn Kelly3, Neil V Marrion3, John A Peters4, Elena Faccenda5, Simon D Harding5,AdamJPawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical -
Nuclear Receptor Assay Applications Presented Fall 2009
Nuclear Receptor Assay Applications Presented Fall 2009 Click the icon in the upper left hand corner to view speaker notes for slides. Have a question? Ask a Scientist GloResponse is a trademark and Dual-Luciferase is a registered trademark of Promega Corporation. HighWire Press is a registered trademark of the Board of Trustees of the Leland Stanford Junior University ©2009, Promega Corporation. All rights reserved. Application Overview POST-TRANSCRIPTION MIRNA CONTROL In vivo PROTEIN applications INTERACTIONS expression level varies with treatment NUCLEAR RECEPTORS SIGNALING Experimental firefly luciferase PATHWAY construct expression level varies little with PROMOTER treatment Control DISSECTION Renilla luciferase construct 2 Traditional Nuclear Receptor Assays Steroid A good assay Works with endogenous receptors Steroid Receptor RNA Pol II NRE luciferase 3 Your expression analysis found an uncharacterized NR… N-Terminal Hinge C-Terminal Domain Region Domain A/B C D E F DNA Binding Ligand Binding Domain Domain •Response elements are not specifically known •Agonists are not known •Coactivators are not known •How can you do work on this nuclear receptor? A One-Hybrid Luciferase Reporter Assay can help understand the nuclear receptor more fully 4 Universal Nuclear Receptor Assays Ligand binding domain responsible for: • homodimerization (class I receptors) • heterodimerization (class II receptors) • corepressor binding • coactivator binding Nuclear Receptor Ligand Binding Domain pBIND Vector GAL4 BD GAL4 GAL4 GAL4 GAL4 GAL4 GAL4 GAL4 -
Anti-Testicular Receptor 2 (TR2) (Rabbit) Antibody - 100-401-E45
Anti-Testicular Receptor 2 (TR2) (Rabbit) Antibody - 100-401-E45 Code: 100-401-E45 Size: 100 µL Product Description: Anti-Testicular Receptor 2 (TR2) (Rabbit) Antibody - 100-401-E45 Concentration: Titrated value sufficient to run approximately 10 mini blots. PhysicalState: Liquid Label Unconjugated Host Rabbit Gene Name NR2C1 Species Reactivity mouse, human, rat Storage Condition Store vial at -20° C prior to opening. This product is stable at 4° C as an undiluted liquid. For extended storage, aliquot contents and freeze at -20° C or below. Avoid cycles of freezing and thawing. Dilute only prior to immediate use. Synonyms Nuclear receptor subfamily 2 group C member 1, Orphan nuclear receptor TR2, mTR2 Application Note Anti-Testicular Receptor 2 (Rabbit) antibody is suitable for use in Western Blots. Anti-Testicular Receptor 2 antibodies are specific for the ~64 kDa TR2 protein in Western blots of testes and nuclear extracts from MEL cell lines. Researchers should determine optimal titers for applications that are not stated below. Background TR2 antibody detects Testicular receptor 2 (TR2), which is a member of the orphan nuclear receptor family. It is widely expressed at a low level throughout the adult testis. TR2 represses transcription and binds DNA directly interacting with HDAC3 and HDAC4 via DNA-binding domains. TR2 has also been implicated in regulation of estrogen receptor activity in mammary glands. In addition, TR2 has recently been shown to form a heterodimer with TR4 that can bind to the direct repeat 6 element of the hepatitis B virus (HBV) enhancer II region thus suppressing HBV gene expression. -
Understanding Nuclear Receptor Form and Function Using Structural Biology
F RASTINEJAD and others Understanding NR form 51:3 T1–T21 Thematic Review and function Understanding nuclear receptor form and function using structural biology Correspondence Fraydoon Rastinejad, Pengxiang Huang, Vikas Chandra and Sepideh Khorasanizadeh should be addressed to F Rastinejad Metabolic Signaling and Disease Program, Sanford-Burnham Medical Research Institute, Orlando, Email Florida 32827, USA frastinejad@ sanfordburnham.org Abstract Nuclear receptors (NRs) are a major transcription factor family whose members selectively Key Words bind small-molecule lipophilic ligands and transduce those signals into specific changes in " nuclear receptors gene programs. For over two decades, structural biology efforts were focused exclusively on " steroid hormones the individual ligand-binding domains (LBDs) or DNA-binding domains of NRs. These " transcription factors analyses revealed the basis for both ligand and DNA binding and also revealed receptor " gene regulation conformations representing both the activated and repressed states. Additionally, " metabolism crystallographic studies explained how NR LBD surfaces recognize discrete portions of transcriptional coregulators. The many structural snapshots of LBDs have also guided the development of synthetic ligands with therapeutic potential. Yet, the exclusive structural focus on isolated NR domains has made it difficult to conceptualize how all the NR polypeptide segments are coordinated physically and functionally in the context of receptor Journal of Molecular Endocrinology quaternary architectures. Newly emerged crystal structures of the peroxisome proliferator- activated receptor-g–retinoid X receptor a (PPARg–RXRa) heterodimer and hepatocyte nuclear factor (HNF)-4a homodimer have recently revealed the higher order organizations of these receptor complexes on DNA, as well as the complexity and uniqueness of their domain–domain interfaces. -
Expression and Role of Nuclear Receptor Coregulators in Colorectal Cancer Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri
Expression and role of nuclear receptor coregulators in colorectal cancer Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri To cite this version: Mouna Triki, Marion Lapierre, Vincent Cavaillès, Raja Mokdad-Gargouri. Expression and role of nuclear receptor coregulators in colorectal cancer. World Journal of Gastroenterology, Baishideng Publishing Group Co. Limited, 2017, 23 (25), pp.4480 - 4490. 10.3748/wjg.v23.i25.4480. inserm- 02438832 HAL Id: inserm-02438832 https://www.hal.inserm.fr/inserm-02438832 Submitted on 14 Jan 2020 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. Submit a Manuscript: http://www.f6publishing.com World J Gastroenterol 2017 July 7; 23(25): 4480-4490 DOI: 10.3748/wjg.v23.i25.4480 ISSN 1007-9327 (print) ISSN 2219-2840 (online) REVIEW Expression and role of nuclear receptor coregulators in colorectal cancer Mouna Triki, Marion Lapierre, Vincent Cavailles, Raja Mokdad-Gargouri Mouna Triki, Marion Lapierre, Vincent Cavailles, IRCM, Peer-review started: August 3, 2016 Institut de Recherche en Cancérologie de -
Characterization of Transcription Factor Complexes Involved in Globin Gene Regulation
Characterization of Transcription Factor Complexes involved in Globin Gene Regulation Katarzyna Ewa Kołodziej 26th March 2008 Cover: Rodota The work presented in this thesis was performed at the Department of Cell Biology at the Erasmus Univer- sity Medical Center Rotterdam. This department is member of the Medisch Genetisch Centrum Zuid-West Nederland. The research was partially supported by the Netherlandse Organizatie voor Wetenschappelijk Onderzoek (NWO) and by EU. Characterization of Transcription Factor Complexes involved in Globin Gene Regulation Karakterizering van transcriptie factor complexen betrokken bij de regulatie van globine genen PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de Rector Magnificus Prof.dr. S.W.J. Lamberts en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 26 maart 2008 om 15.45 uur. door Katarzyna Ewa Kołodziej geboren te Wrocław, Polen Promotiecommissie Promotor: Prof.dr. F.G. Grosveld Overige laden: Prof.dr. J.N.J. Philipsen Prof.dr. J.D. Engel Dr.ir. D.N. Meijer Copromotor: Dr. J. Strouboulis Moim rodzicom & for Luc TABLE OF CONTENTS Chapter 1 : Introduction 9 Chapter 2 : Isolation of transcription factor complexes by in vivo biotinylation tagging and direct binding to streptavidin beads (Patrick Rodriguez, Harald Braun, Katarzyna E. Kolodziej, Ernie de Boer, Jennifer Campbel, Edgar Bonte, Sjaak Philipsen and John Strouboulis Methods Mol Bio. 2006; 338: 305-23 ) 33 Chapter 3 : GATA-1 forms distinct activating and repressive complexes in erythroid cells (Patrick Rodriguez, Edgar Bonte, Jeroen Krijgsveld, Katarzyna E. Kolodziej, Boris Guyot, Albert Heck, Paresh Vyas, Ernie de Boer, Frank Grosveld and John Strouboulis, EMBO J. -
Recent Advances in Understanding Corticotroph Pituitary Tumor Initiation and Progression [Version 1; Peer Review: 2 Approved] Ulrich Renner , Denis Ciato , Günter K
F1000Research 2018, 7(F1000 Faculty Rev):1354 Last updated: 17 JUL 2019 REVIEW Recent advances in understanding corticotroph pituitary tumor initiation and progression [version 1; peer review: 2 approved] Ulrich Renner , Denis Ciato , Günter K. Stalla Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Munich, Germany First published: 29 Aug 2018, 7(F1000 Faculty Rev):1354 ( Open Peer Review v1 https://doi.org/10.12688/f1000research.14789.1) Latest published: 29 Aug 2018, 7(F1000 Faculty Rev):1354 ( https://doi.org/10.12688/f1000research.14789.1) Reviewer Status Abstract Invited Reviewers Cushing’s disease is the most frequent form of hypercortisolism and is 1 2 caused by hypophyseal corticotroph adenomas secreting excessive amounts of adrenocorticotropic hormone. Most of the tumors develop version 1 sporadically and only a limited number of corticotroph adenomas have published been found to be associated with different neuroendocrine syndromes or 29 Aug 2018 with familial isolated pituitary adenomas. The pathogenic mechanisms of corticotroph adenomas are largely unknown, but the discovered aberrant chaperoning activity of heat shock protein 90 on the one hand and the F1000 Faculty Reviews are written by members of presence of ubiquitin-specific protease 8 mutations on the other hand the prestigious F1000 Faculty. They are partially explained the causes of their development. Corticotroph tumors commissioned and are peer reviewed before arise initially as benign microadenomas but with time form invasively publication to ensure that the final, published version growing aggressive macroadenomas which can switch to corticotroph carcinomas in extremely rare cases. The mechanisms through which is comprehensive and accessible. The reviewers corticotroph tumors escape from glucocorticoid negative feedback are still who approved the final version are listed with their poorly understood, as are the processes that trigger the progression of names and affiliations.