Ing1 Functions in DNA Demethylation by Directing Gadd45a to H3k4me3
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Expression Pattern and Level of ING5 Protein in Normal and Cancer Tissues
ONCOLOGY LETTERS 17: 63-68, 2019 Expression pattern and level of ING5 protein in normal and cancer tissues XUE-FENG YANG1, DAO-FU SHEN1, SHUANG ZHAO1, TIAN-REN REN2, YANG GAO1, SHUAI SHI1, JI-CHENG WU1, HONG-ZHI SUN1 and HUA-CHUAN ZHENG1,3 1Cancer Center and Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001;2 Jilin Province Forestry Bureau, Linjiang, Jilin 134600; 3Institute of Life Sciences, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China Received February 21, 2016; Accepted February 13, 2017 DOI: 10.3892/ol.2018.9581 Abstract. Inhibitor of growth family 5 (ING5) functions as may be involved in cell regeneration and be associated with a type-II tumor suppressor gene and exerts an important role colorectal carcinogenesis. in DNA repair, apoptotic induction, proliferative inhibition, chromatin remodeling and the invasion process. In the present Introduction study, immunohistochemistry was performed to characterize the expression profile of ING5 protein on a tissue microarray Inhibitor of growth family 5 (ING5) is a member of the ING containing mouse and human normal tissues, and human protein family and functions as a type-II tumor suppressor cancer tissues, including hepatocellular (n=62), renal clear cell gene. Human ING5 is mapped to chromosome 2q37.3 and (n=62), pancreatic (n=62), esophageal squamous cell (n=45), encodes a 28-kDa protein with 240 amino acids (1). As indi- cervical squamous cell (n=31), breast (n=144), gastric (n=196), cated in Fig. 1, ING5 protein consists of a number of domains, colorectal (n=96), endometrial (n=96) and lung carcinoma including leucine zipper like (LZL), novel conserved region (n=192). -
Analysis of Gene Expression Data for Gene Ontology
ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION A Thesis Presented to The Graduate Faculty of The University of Akron In Partial Fulfillment of the Requirements for the Degree Master of Science Robert Daniel Macholan May 2011 ANALYSIS OF GENE EXPRESSION DATA FOR GENE ONTOLOGY BASED PROTEIN FUNCTION PREDICTION Robert Daniel Macholan Thesis Approved: Accepted: _______________________________ _______________________________ Advisor Department Chair Dr. Zhong-Hui Duan Dr. Chien-Chung Chan _______________________________ _______________________________ Committee Member Dean of the College Dr. Chien-Chung Chan Dr. Chand K. Midha _______________________________ _______________________________ Committee Member Dean of the Graduate School Dr. Yingcai Xiao Dr. George R. Newkome _______________________________ Date ii ABSTRACT A tremendous increase in genomic data has encouraged biologists to turn to bioinformatics in order to assist in its interpretation and processing. One of the present challenges that need to be overcome in order to understand this data more completely is the development of a reliable method to accurately predict the function of a protein from its genomic information. This study focuses on developing an effective algorithm for protein function prediction. The algorithm is based on proteins that have similar expression patterns. The similarity of the expression data is determined using a novel measure, the slope matrix. The slope matrix introduces a normalized method for the comparison of expression levels throughout a proteome. The algorithm is tested using real microarray gene expression data. Their functions are characterized using gene ontology annotations. The results of the case study indicate the protein function prediction algorithm developed is comparable to the prediction algorithms that are based on the annotations of homologous proteins. -
The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3k4me3 Mark
Article The Tumor Suppressor ING5 Is a Dimeric, Bivalent Recognition Molecule of the Histone H3K4me3 Mark Georgina Ormaza 1,†, Jhon A. Rodríguez 1,†, Alain Ibáñez de Opakua 1, Nekane Merino 1, Maider Villate 1, Irantzu Gorroño 1, Miriam Rábano 1, Ignacio Palmero 2, Marta Vilaseca 3, Robert Kypta 1,4, María d.M. Vivanco 1, Adriana L. Rojas 1 and Francisco J. Blanco 1,5 1 - CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Spain 2 - Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, 28029 Madrid, Spain 3 - Institute for Research in Biomedicine, 08028 Barcelona, Spain 4 - Department of Surgery and Cancer, Imperial College London, London, W12 0NN, UK 5 - IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain Correspondence to Francisco J. Blanco: CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Spain. [email protected] https://doi.org/10.1016/j.jmb.2019.04.018 Edited by M. Guss Abstract The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at lysine 4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus of the five ING proteins. ING5 facilitates histone H3 acetylation by the HBO1 complex, and also H4 acetylation by the MOZ/ MORF complex. We show that ING5 forms homodimers through its N-terminal domain, which folds independently into an elongated coiled-coil structure. The central region of ING5, which contains the nuclear localization sequence, is flexible and disordered, but it binds dsDNA with micromolar affinity. NMR analysis of the full-length protein reveals that the two PHD fingers of the dimer are chemically equivalent and independent of the rest of the molecule, and they bind H3K4me3 in the same way as the isolated PHD. -
Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin
cells Review Modes of Interaction of KMT2 Histone H3 Lysine 4 Methyltransferase/COMPASS Complexes with Chromatin Agnieszka Bochy ´nska,Juliane Lüscher-Firzlaff and Bernhard Lüscher * ID Institute of Biochemistry and Molecular Biology, Medical School, RWTH Aachen University, Pauwelsstrasse 30, 52057 Aachen, Germany; [email protected] (A.B.); jluescher-fi[email protected] (J.L.-F.) * Correspondence: [email protected]; Tel.: +49-241-8088850; Fax: +49-241-8082427 Received: 18 January 2018; Accepted: 27 February 2018; Published: 2 March 2018 Abstract: Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes. The latter includes modulating the composition of core histones and their variants that are integrated into nucleosomes, and the post-translational modification of these histones referred to as histone marks. One of these marks is the methylation of lysine 4 of the core histone H3 (H3K4). While mono-methylation of H3K4 (H3K4me1) is located preferentially at active enhancers, tri-methylation (H3K4me3) is a mark found at open and potentially active promoters. Thus, H3K4 methylation is typically associated with gene transcription. The class 2 lysine methyltransferases (KMTs) are the main enzymes that methylate H3K4. KMT2 enzymes function in complexes that contain a necessary core complex composed of WDR5, RBBP5, ASH2L, and DPY30, the so-called WRAD complex. -
Network Assessment of Demethylation Treatment in Melanoma: Differential Transcriptome-Methylome and Antigen Profile Signatures
RESEARCH ARTICLE Network assessment of demethylation treatment in melanoma: Differential transcriptome-methylome and antigen profile signatures Zhijie Jiang1☯, Caterina Cinti2☯, Monia Taranta2, Elisabetta Mattioli3,4, Elisa Schena3,5, Sakshi Singh2, Rimpi Khurana1, Giovanna Lattanzi3,4, Nicholas F. Tsinoremas1,6, 1 Enrico CapobiancoID * a1111111111 1 Center for Computational Science, University of Miami, Miami, FL, United States of America, 2 Institute of Clinical Physiology, CNR, Siena, Italy, 3 CNR Institute of Molecular Genetics, Bologna, Italy, 4 IRCCS Rizzoli a1111111111 Orthopedic Institute, Bologna, Italy, 5 Endocrinology Unit, Department of Medical & Surgical Sciences, Alma a1111111111 Mater Studiorum University of Bologna, S Orsola-Malpighi Hospital, Bologna, Italy, 6 Department of a1111111111 Medicine, University of Miami, Miami, FL, United States of America a1111111111 ☯ These authors contributed equally to this work. * [email protected] OPEN ACCESS Abstract Citation: Jiang Z, Cinti C, Taranta M, Mattioli E, Schena E, Singh S, et al. (2018) Network assessment of demethylation treatment in Background melanoma: Differential transcriptome-methylome and antigen profile signatures. PLoS ONE 13(11): In melanoma, like in other cancers, both genetic alterations and epigenetic underlie the met- e0206686. https://doi.org/10.1371/journal. astatic process. These effects are usually measured by changes in both methylome and pone.0206686 transcriptome profiles, whose cross-correlation remains uncertain. We aimed to assess at Editor: Roger Chammas, Universidade de Sao systems scale the significance of epigenetic treatment in melanoma cells with different met- Paulo, BRAZIL astatic potential. Received: June 20, 2018 Accepted: October 17, 2018 Methods and findings Published: November 28, 2018 Treatment by DAC demethylation with 5-Aza-2'-deoxycytidine of two melanoma cell lines Copyright: © 2018 Jiang et al. -
The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells
University of Calgary PRISM: University of Calgary's Digital Repository Graduate Studies The Vault: Electronic Theses and Dissertations 2016 The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells Wang, Fangwu Jr Wang, F. J. (2016). The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells (Unpublished master's thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/28327 http://hdl.handle.net/11023/3233 master thesis University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. Downloaded from PRISM: https://prism.ucalgary.ca UNIVERSITY OF CALGARY The Role of ING5 in Maintaining Stemness of Brain Tumor Initiating Cells by Fangwu Wang A THESIS SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE GRADUATE PROGRAM IN BIOCHEMISTRY AND MOLECULAR BIOLOGY CALGARY, ALBERTA AUGUST, 2016 © Fangwu Wang 2016 Abstract Brain tumor initiating cells (BTICs) are believed to account for the recurrence of glioblastomas following treatment. Recent studies have shown that the stemness of BTICs and intratumoral differentiation hierarchy are determined largely on the epigenetic level. The ING family of epigenetic regulators function in diverse growth regulatory, metastasis and chemoresistance pathways, through targeting different histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes to the H3K4me3 mark to alter histone acetylation. -
1 a Search for Novel Cancer/Testis Antigens in Lung Cancer Identifies
Author Manuscript Published OnlineFirst on June 26, 2014; DOI: 10.1158/0008-5472.CAN-13-3725 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. A search for novel cancer/testis antigens in lung cancer identifies VCX/Y genes expanding the repertoire of potential immunotherapeutic targets Ayumu Taguchi1*, Allen D. Taylor2, Jaime Rodriguez1, Müge Çeliktaş3, Hui Liu1, Xiaotu Ma4, Qing Zhang2, Chee-Hong Wong2, Alice Chin2, Luc Girard5,6, Carmen Behrens7, Wan L. Lam8, Stephen Lam8, John D. Minna5,6,9, Ignacio I. Wistuba1, Adi F. Gazdar5,10, and Samir M. Hanash3 1Departments of Translational Molecular Pathology, 3Clinical Cancer Prevention, and 7Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA 2Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA 4Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas Southwestern Medical Center at Dallas, 800 W. Campbell Road, Dallas, TX 75080, USA 5Hamon Center for Therapeutic Oncology Research and Departments of 6Pharmacology, 9Internal Medicine, and 10Pathology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390, USA 8Department of Integrative Oncology, British Columbia Cancer Research Centre, 675 West 10th Avenue, Vancouver, BC V521L3, Canada Corresponding Author: *Correspondence should be addressed to Ayumu Taguchi, Department of Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; email: [email protected]; fax: 713-563-5746; phone: 713-563-8069. 1 Downloaded from cancerres.aacrjournals.org on September 24, 2021. -
MAGEB2 (NM 002364) Human Tagged ORF Clone – RG205338
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for RG205338 MAGEB2 (NM_002364) Human Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: MAGEB2 (NM_002364) Human Tagged ORF Clone Tag: TurboGFP Symbol: MAGEB2 Synonyms: CT3.2; DAM6; MAGE-XP-2 Vector: pCMV6-AC-GFP (PS100010) E. coli Selection: Ampicillin (100 ug/mL) Cell Selection: Neomycin ORF Nucleotide >RG205338 representing NM_002364 Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGCCTCGTGGTCAGAAGAGTAAGCTCCGTGCCCGTGAGAAACGCCGCAAGGCCCGAGATGAGACCCGGG GTCTCAATGTTCCTCAGGTCACTGAAGCAGAGGAAGAAGAGGCCCCCTGCTGTTCCTCTTCTGTTTCTGG GGGTGCTGCTTCAAGCTCTCCTGCTGCTGGCATTCCCCAGAAGCCTCAGAGAGCCCCAACCACTGCCGCT GCTGCAGCTGCGGGTGTTTCATCCACAAAATCTAAAAAAGGTGCCAAGAGCCACCAAGGTGAGAAAAATG CAAGTTCCTCCCAGGCCTCAACATCTACTAAGAGCCCAAGCGAAGATCCTCTAACCAGGAAGTCAGGGTC GTTGGTGCAGTTCCTGTTGTACAAGTATAAAATAAAAAAGTCCGTTACAAAGGGAGAAATGCTGAAAATT GTTGGCAAAAGGTTCAGGGAGCACTTCCCTGAGATCCTCAAGAAAGCCTCTGAGGGCCTCAGTGTTGTCT TTGGCCTTGAGCTGAATAAAGTCAACCCCAACGGCCACACTTACACCTTCATCGACAAGGTAGACCTCAC TGATGAGGAATCCCTGCTCAGTTCCTGGGACTTTCCCAGGAGAAAGCTTCTGATGCCTCTCCTGGGTGTG ATCTTCTTAAATGGCAACTCAGCTACTGAGGAAGAGATCTGGGAATTCCTGAATATGTTGGGAGTCTATG ATGGAGAGGAGCACTCAGTCTTTGGGGAACCCTGGAAGCTCATCACCAAAGATCTGGTGCAGGAAAAATA TCTGGAGTACAAGCAGGTGCCCAGCAGTGATCCCCCACGCTTTCAATTCCTGTGGGGTCCGAGAGCCTAT GCTGAAACCAGCAAGATGAAAGTCCTGGAGTTTTTGGCCAAGGTAAATGGTACCACCCCCTGTGCCTTCC -
Molecular Mechanisms of Ribosomal Protein Gene Coregulation
Downloaded from genesdev.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Molecular mechanisms of ribosomal protein gene coregulation Rohit Reja, Vinesh Vinayachandran, Sujana Ghosh, and B. Franklin Pugh Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, Pennsylvania 16802, USA The 137 ribosomal protein genes (RPGs) of Saccharomyces provide a model for gene coregulation. We examined the positional and functional organization of their regulators (Rap1 [repressor activator protein 1], Fhl1, Ifh1, Sfp1, and Hmo1), the transcription machinery (TFIIB, TFIID, and RNA polymerase II), and chromatin at near-base-pair res- olution using ChIP-exo, as RPGs are coordinately reprogrammed. Where Hmo1 is enriched, Fhl1, Ifh1, Sfp1, and Hmo1 cross-linked broadly to promoter DNA in an RPG-specific manner and demarcated by general minor groove widening. Importantly, Hmo1 extended 20–50 base pairs (bp) downstream from Fhl1. Upon RPG repression, Fhl1 remained in place. Hmo1 dissociated, which was coupled to an upstream shift of the +1 nucleosome, as reflected by the Hmo1 extension and core promoter region. Fhl1 and Hmo1 may create two regulatable and positionally distinct barriers, against which chromatin remodelers position the +1 nucleosome into either an activating or a repressive state. Consistent with in vitro studies, we found that specific TFIID subunits, in addition to cross-linking at the core promoter, made precise cross-links at Rap1 sites, which we interpret to reflect native Rap1–TFIID interactions. Our findings suggest how sequence-specific DNA binding regulates nucleosome positioning and transcription complex assembly >300 bp away and how coregulation coevolved with coding sequences. -
Novel Candidate Genes of Thyroid Tumourigenesis Identified in Trk-T1 Transgenic Mice
Endocrine-Related Cancer (2012) 19 409–421 Novel candidate genes of thyroid tumourigenesis identified in Trk-T1 transgenic mice Katrin-Janine Heiliger*, Julia Hess*, Donata Vitagliano1, Paolo Salerno1, Herbert Braselmann, Giuliana Salvatore 2, Clara Ugolini 3, Isolde Summerer 4, Tatjana Bogdanova5, Kristian Unger 6, Gerry Thomas6, Massimo Santoro1 and Horst Zitzelsberger Research Unit of Radiation Cytogenetics, Helmholtz Zentrum Mu¨nchen, Ingolsta¨dter Landstr. 1, 85764 Neuherberg, Germany 1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita` Federico II, Naples 80131, Italy 2Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Universita` ‘Parthenope’, Naples 80133, Italy 3Division of Pathology, Department of Surgery, University of Pisa, 56100 Pisa, Italy 4Institute of Radiation Biology, Helmholtz Zentrum Mu¨nchen, 85764 Neuherberg, Germany 5Institute of Endocrinology and Metabolism, Academy of Medical Sciences of the Ukraine, 254114 Kiev, Ukraine 6Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London W12 0HS, UK (Correspondence should be addressed to H Zitzelsberger; Email: [email protected]) *(K-J Heiliger and J Hess contributed equally to this work) Abstract For an identification of novel candidate genes in thyroid tumourigenesis, we have investigated gene copy number changes in a Trk-T1 transgenic mouse model of thyroid neoplasia. For this aim, 30 thyroid tumours from Trk-T1 transgenics were investigated by comparative genomic hybridisation. Recurrent gene copy number alterations were identified and genes located in the altered chromosomal regions were analysed by Gene Ontology term enrichment analysis in order to reveal gene functions potentially associated with thyroid tumourigenesis. In thyroid neoplasms from Trk-T1 mice, a recurrent gain on chromosomal bands 1C4–E2.3 (10.0% of cases), and losses on 3H1–H3 (13.3%), 4D2.3–E2 (43.3%) and 14E4–E5 (6.7%) were identified. -
Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways
biomolecules Article Whole Genome Sequencing of Familial Non-Medullary Thyroid Cancer Identifies Germline Alterations in MAPK/ERK and PI3K/AKT Signaling Pathways Aayushi Srivastava 1,2,3,4 , Abhishek Kumar 1,5,6 , Sara Giangiobbe 1, Elena Bonora 7, Kari Hemminki 1, Asta Försti 1,2,3 and Obul Reddy Bandapalli 1,2,3,* 1 Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany; [email protected] (A.S.); [email protected] (A.K.); [email protected] (S.G.); [email protected] (K.H.); [email protected] (A.F.) 2 Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany 3 Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany 4 Medical Faculty, Heidelberg University, D-69120 Heidelberg, Germany 5 Institute of Bioinformatics, International Technology Park, Bangalore 560066, India 6 Manipal Academy of Higher Education (MAHE), Manipal, Karnataka 576104, India 7 S.Orsola-Malphigi Hospital, Unit of Medical Genetics, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected]; Tel.: +49-6221-42-1709 Received: 29 August 2019; Accepted: 10 October 2019; Published: 13 October 2019 Abstract: Evidence of familial inheritance in non-medullary thyroid cancer (NMTC) has accumulated over the last few decades. However, known variants account for a very small percentage of the genetic burden. Here, we focused on the identification of common pathways and networks enriched in NMTC families to better understand its pathogenesis with the final aim of identifying one novel high/moderate-penetrance germline predisposition variant segregating with the disease in each studied family. -
TAF10 Complex Provides Evidence for Nuclear Holo&Ndash;TFIID Assembly from Preform
ARTICLE Received 13 Aug 2014 | Accepted 2 Dec 2014 | Published 14 Jan 2015 DOI: 10.1038/ncomms7011 OPEN Cytoplasmic TAF2–TAF8–TAF10 complex provides evidence for nuclear holo–TFIID assembly from preformed submodules Simon Trowitzsch1,2, Cristina Viola1,2, Elisabeth Scheer3, Sascha Conic3, Virginie Chavant4, Marjorie Fournier3, Gabor Papai5, Ima-Obong Ebong6, Christiane Schaffitzel1,2, Juan Zou7, Matthias Haffke1,2, Juri Rappsilber7,8, Carol V. Robinson6, Patrick Schultz5, Laszlo Tora3 & Imre Berger1,2,9 General transcription factor TFIID is a cornerstone of RNA polymerase II transcription initiation in eukaryotic cells. How human TFIID—a megadalton-sized multiprotein complex composed of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs)— assembles into a functional transcription factor is poorly understood. Here we describe a heterotrimeric TFIID subcomplex consisting of the TAF2, TAF8 and TAF10 proteins, which assembles in the cytoplasm. Using native mass spectrometry, we define the interactions between the TAFs and uncover a central role for TAF8 in nucleating the complex. X-ray crystallography reveals a non-canonical arrangement of the TAF8–TAF10 histone fold domains. TAF2 binds to multiple motifs within the TAF8 C-terminal region, and these interactions dictate TAF2 incorporation into a core–TFIID complex that exists in the nucleus. Our results provide evidence for a stepwise assembly pathway of nuclear holo–TFIID, regulated by nuclear import of preformed cytoplasmic submodules. 1 European Molecular Biology Laboratory, Grenoble Outstation, 6 rue Jules Horowitz, 38042 Grenoble, France. 2 Unit for Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 6 rue Jules Horowitz, 38042 Grenoble, France. 3 Cellular Signaling and Nuclear Dynamics Program, Institut de Ge´ne´tique et de Biologie Mole´culaire et Cellulaire, UMR 7104, INSERM U964, 1 rue Laurent Fries, 67404 Illkirch, France.