Table S3: Subset of Zebrafish Early Genes with Human And
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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. -
Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-Like Mouse Models: Tracking the Role of the Hairless Gene
University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 5-2006 Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene Yutao Liu University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Life Sciences Commons Recommended Citation Liu, Yutao, "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino- like Mouse Models: Tracking the Role of the Hairless Gene. " PhD diss., University of Tennessee, 2006. https://trace.tennessee.edu/utk_graddiss/1824 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Yutao Liu entitled "Molecular and Physiological Basis for Hair Loss in Near Naked Hairless and Oak Ridge Rhino-like Mouse Models: Tracking the Role of the Hairless Gene." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Life Sciences. Brynn H. Voy, Major Professor We have read this dissertation and recommend its acceptance: Naima Moustaid-Moussa, Yisong Wang, Rogert Hettich Accepted for the Council: Carolyn R. -
A Rare Variant in MCF2L Identified Using Exclusion Linkage in A
European Journal of Human Genetics (2016) 24, 86–91 & 2016 Macmillan Publishers Limited All rights reserved 1018-4813/16 www.nature.com/ejhg ARTICLE A rare variant in MCF2L identified using exclusion linkage in a pedigree with premature atherosclerosis Stephanie Maiwald1,7, Mahdi M Motazacker1,7,8, Julian C van Capelleveen1, Suthesh Sivapalaratnam1, Allard C van der Wal2, Chris van der Loos2, John JP Kastelein1, Willem H Ouwehand3,4, G Kees Hovingh1, Mieke D Trip1,5, Jaap D van Buul6 and Geesje M Dallinga-Thie*,1 Cardiovascular disease (CVD) is a major cause of death in Western societies. CVD risk is largely genetically determined. The molecular pathology is, however, not elucidated in a large number of families suffering from CVD. We applied exclusion linkage analysis and next-generation sequencing to elucidate the molecular defect underlying premature CVD in a small pedigree, comprising two generations of which six members suffered from premature CVD. A total of three variants showed co-segregation with the disease status in the family. Two of these variants were excluded from further analysis based on the prevalence in replication cohorts, whereas a non-synonymous variant in MCF.2 Cell Line Derived Transforming Sequence-like protein (MCF2L, c.2066A4G; p.(Asp689Gly); NM_001112732.1), located in the DH domain, was only present in the studied family. MCF2L is a guanine exchange factor that potentially links pathways that signal through Rac1 and RhoA. Indeed, in HeLa cells, MCF2L689Gly failed to activate Rac1 as well as RhoA, resulting in impaired stress fiber formation. Moreover, MCF2L protein was found in human atherosclerotic lesions but not in healthy tissue segments. -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
CCT6A Sirna (Mouse)
For research purposes only, not for human use Product Data Sheet CCT6A siRNA (Mouse) Catalog # Source Reactivity Applications CRM0566 Synthetic M RNAi Description siRNA to inhibit CCT6A expression using RNA interference Specificity CCT6A siRNA (Mouse) is a target-specific 19-23 nt siRNA oligo duplexes designed to knock down gene expression. Form Lyophilized powder Gene Symbol CCT6A Alternative Names CCT6; CCTZ; CCTZ1; T-complex protein 1 subunit zeta; TCP-1-zeta; CCT-zeta-1 Entrez Gene 12466 (Mouse) SwissProt P80317 (Mouse) Purity > 97% Quality Control Oligonucleotide synthesis is monitored base by base through trityl analysis to ensure appropriate coupling efficiency. The oligo is subsequently purified by affinity-solid phase extraction. The annealed RNA duplex is further analyzed by mass spectrometry to verify the exact composition of the duplex. Each lot is compared to the previous lot by mass spectrometry to ensure maximum lot-to-lot consistency. Components We offers pre-designed sets of 3 different target-specific siRNA oligo duplexes of mouse CCT6A gene. Each vial contains 5 nmol of lyophilized siRNA. The duplexes can be transfected individually or pooled together to achieve knockdown of the target gene, which is most commonly assessed by qPCR or western blot. Our siRNA oligos are also chemically modified (2’-OMe) at no extra charge for increased stability and enhanced knockdown in vitro and in vivo. Directions for Use We recommends transfection with 100 nM siRNA 48 to 72 hours prior to cell lysis. Application key: E- ELISA, WB- -
Overexpressing CCT6A Contributes to Cancer Cell Growth by Affecting the G1-To-S Phase Transition and Predicts a Negative Prognosis in Hepatocellular Carcinoma
OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Overexpressing CCT6A Contributes To Cancer Cell Growth By Affecting The G1-To-S Phase Transition And Predicts A Negative Prognosis In Hepatocellular Carcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy Guofen Zeng1,* Purpose: To determine the oncogenic role of the sixth subunit of chaperonin-containing Jialiang Wang2,* tailless complex polypeptide 1 (CCT6A) in hepatocellular carcinoma (HCC) and address the Yanlin Huang 1,* correlation of CCT6A with clinicopathological characteristics and survival. Additionally, this Yifan Lian 2 study aimed to explore the effect of CCT6A on HCC cells and the underlying mechanisms. Dongmei Chen2 Methods: We searched for levels of CCT6A expression in the Oncomine database and GEPIA database, which was then validated by analyzing cancer and adjacent non-cancerous Huan Wei 2 tissues of HCC patients using quantitative PCR, Western blot, and immunohistochemistry Chaoshuang Lin1 1,2 assays. The relationship between CCT6A expression and survival was analyzed from the Yuehua Huang GEPIA database and confirmed by immunohistochemistry assays of 133 HCC tissue sec- 1Department of Infectious Diseases, The tions. In addition, the effect of depleting CCT6A on cell proliferation was assessed by CCK- fi Third Af liated Hospital of Sun Yat-sen 8 and colony formation assays. Cell cycle analysis, immunofluorescence assays, GSEA University, Guangzhou 510630, Guangdong, People’s Republic of China; analysis, and cyclin D expression analyzed by Western blot were used to explore the possible 2Guangdong Provincial Key Laboratory of underlying mechanism how dysregulated CCT6A affect the proliferation of HCC. -
Open Full Page
Published OnlineFirst February 10, 2017; DOI: 10.1158/2159-8290.CD-16-1045 RESEARCH ARTICLE Interaction Landscape of Inherited Polymorphisms with Somatic Events in Cancer Hannah Carter 1 , 2 , 3 , 4 , Rachel Marty 5 , Matan Hofree 6 , Andrew M. Gross 5 , James Jensen 5 , Kathleen M. Fisch1,2,3,7 , Xingyu Wu 2 , Christopher DeBoever 5 , Eric L. Van Nostrand 4,8 , Yan Song 4,8 , Emily Wheeler 4,8 , Jason F. Kreisberg 1,3 , Scott M. Lippman 2 , Gene W. Yeo 4,8 , J. Silvio Gutkind 2 , 3 , and Trey Ideker 1 , 2 , 3 , 4 , 5,6 Downloaded from cancerdiscovery.aacrjournals.org on September 27, 2021. © 2017 American Association for Cancer Research. Published OnlineFirst February 10, 2017; DOI: 10.1158/2159-8290.CD-16-1045 ABSTRACT Recent studies have characterized the extensive somatic alterations that arise dur- ing cancer. However, the somatic evolution of a tumor may be signifi cantly affected by inherited polymorphisms carried in the germline. Here, we analyze genomic data for 5,954 tumors to reveal and systematically validate 412 genetic interactions between germline polymorphisms and major somatic events, including tumor formation in specifi c tissues and alteration of specifi c cancer genes. Among germline–somatic interactions, we found germline variants in RBFOX1 that increased incidence of SF3B1 somatic mutation by 8-fold via functional alterations in RNA splicing. Similarly, 19p13.3 variants were associated with a 4-fold increased likelihood of somatic mutations in PTEN. In support of this associ- ation, we found that PTEN knockdown sensitizes the MTOR pathway to high expression of the 19p13.3 gene GNA11 . -
CCT6A Rabbit Pab
Leader in Biomolecular Solutions for Life Science CCT6A Rabbit pAb Catalog No.: A3589 1 Publications Basic Information Background Catalog No. The protein encoded by this gene is a molecular chaperone that is a member of the A3589 chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different Observed MW proteins. Unfolded polypeptides enter the central cavity of the complex and are folded 58kDa in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants of this gene, encoding different Calculated MW isoforms, have been characterized. In addition, several pseudogenes of this gene have 53kDa/58kDa been located. Category Primary antibody Applications WB,IHC Cross-Reactivity Human, Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 908 P40227 IHC 1:50 - 1:100 Immunogen Recombinant fusion protein containing a sequence corresponding to amino acids 80-250 of human CCT6A (NP_001753.1). Synonyms CCT6A;CCT-zeta;CCT-zeta-1;CCT6;Cctz;HTR3;MoDP-2;TCP-1-zeta;TCP20;TCPZ;TTCP20 Contact Product Information www.abclonal.com Source Isotype Purification Rabbit IgG Affinity purification Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using CCT6A antibody (A3589) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. -
A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family
Rockefeller University Digital Commons @ RU Student Theses and Dissertations 2018 A High-Throughput Approach to Uncover Novel Roles of APOBEC2, a Functional Orphan of the AID/APOBEC Family Linda Molla Follow this and additional works at: https://digitalcommons.rockefeller.edu/ student_theses_and_dissertations Part of the Life Sciences Commons A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy by Linda Molla June 2018 © Copyright by Linda Molla 2018 A HIGH-THROUGHPUT APPROACH TO UNCOVER NOVEL ROLES OF APOBEC2, A FUNCTIONAL ORPHAN OF THE AID/APOBEC FAMILY Linda Molla, Ph.D. The Rockefeller University 2018 APOBEC2 is a member of the AID/APOBEC cytidine deaminase family of proteins. Unlike most of AID/APOBEC, however, APOBEC2’s function remains elusive. Previous research has implicated APOBEC2 in diverse organisms and cellular processes such as muscle biology (in Mus musculus), regeneration (in Danio rerio), and development (in Xenopus laevis). APOBEC2 has also been implicated in cancer. However the enzymatic activity, substrate or physiological target(s) of APOBEC2 are unknown. For this thesis, I have combined Next Generation Sequencing (NGS) techniques with state-of-the-art molecular biology to determine the physiological targets of APOBEC2. Using a cell culture muscle differentiation system, and RNA sequencing (RNA-Seq) by polyA capture, I demonstrated that unlike the AID/APOBEC family member APOBEC1, APOBEC2 is not an RNA editor. Using the same system combined with enhanced Reduced Representation Bisulfite Sequencing (eRRBS) analyses I showed that, unlike the AID/APOBEC family member AID, APOBEC2 does not act as a 5-methyl-C deaminase. -
Novel Targets of Apparently Idiopathic Male Infertility
International Journal of Molecular Sciences Review Molecular Biology of Spermatogenesis: Novel Targets of Apparently Idiopathic Male Infertility Rossella Cannarella * , Rosita A. Condorelli , Laura M. Mongioì, Sandro La Vignera * and Aldo E. Calogero Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy; [email protected] (R.A.C.); [email protected] (L.M.M.); [email protected] (A.E.C.) * Correspondence: [email protected] (R.C.); [email protected] (S.L.V.) Received: 8 February 2020; Accepted: 2 March 2020; Published: 3 March 2020 Abstract: Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm-oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility. Keywords: spermatogenetic failure; embryo growth; male infertility; spermatogenesis; recurrent pregnancy loss; sperm proteome; DNA fragmentation; sperm transcriptome 1. Introduction Infertility is a widespread condition in industrialized countries, affecting up to 15% of couples of childbearing age [1]. It is defined as the inability to achieve conception after 1–2 years of unprotected sexual intercourse [2]. -
New Insights on Human Essential Genes Based on Integrated Multi
bioRxiv preprint doi: https://doi.org/10.1101/260224; this version posted February 5, 2018. 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. New insights on human essential genes based on integrated multi- omics analysis Hebing Chen1,2, Zhuo Zhang1,2, Shuai Jiang 1,2, Ruijiang Li1, Wanying Li1, Hao Li1,* and Xiaochen Bo1,* 1Beijing Institute of Radiation Medicine, Beijing 100850, China. 2 Co-first author *Correspondence: [email protected]; [email protected] Abstract Essential genes are those whose functions govern critical processes that sustain life in the organism. Comprehensive understanding of human essential genes could enable breakthroughs in biology and medicine. Recently, there has been a rapid proliferation of technologies for identifying and investigating the functions of human essential genes. Here, according to gene essentiality, we present a global analysis for comprehensively and systematically elucidating the genetic and regulatory characteristics of human essential genes. We explain why these genes are essential from the genomic, epigenomic, and proteomic perspectives, and we discuss their evolutionary and embryonic developmental properties. Importantly, we find that essential human genes can be used as markers to guide cancer treatment. We have developed an interactive web server, the Human Essential Genes Interactive Analysis Platform (HEGIAP) (http://sysomics.com/HEGIAP/), which integrates abundant analytical tools to give a global, multidimensional interpretation of gene essentiality. bioRxiv preprint doi: https://doi.org/10.1101/260224; this version posted February 5, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
CCT6A Suppresses SMAD2 and Promotes Prometastatic TGF-Β Signaling
The Journal of Clinical Investigation RESEARCH ARTICLE CCT6A suppresses SMAD2 and promotes prometastatic TGF-β signaling Zhe Ying,1,2 Han Tian,1,2 Yun Li,1,2 Rong Lian,1,2 Wei Li,1,2 Shanshan Wu,1,2 Hui-Zhong Zhang,3 Jueheng Wu,1,2 Lei Liu,1,2 Junwei Song,2,4 Hongyu Guan,5 Junchao Cai,1,2 Xun Zhu,1,2 Jun Li,2,4 and Mengfeng Li1,2 1Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. 2Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Chinese Ministry of Education, Guangzhou, Guangdong, China. 3Department of Cardiothoracic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. 4Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. 5Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Paradoxically, during early tumor development in many cancer types, TGF-β acts as a tumor suppressor, whereas in the advanced stages of these cancers, increased TGF-β expression is linked to high metastasis and poor prognosis. These findings suggest that unidentified mechanisms may function to rewire TGF-β signaling toward its prometastatic role in cancer cells. Our current study using non–small-cell lung carcinoma (NSCLC) cell lines, animal models, and clinical specimens demonstrates that suppression of SMAD2, with SMAD3 function intact, switches TGF-β–induced transcriptional responses to a prometastatic state. Importantly, we identified chaperonin containing TCP1 subunit 6A (CCT6A) as an inhibitor and direct binding protein of SMAD2 and found that CCT6A suppresses SMAD2 function in NSCLC cells and promotes metastasis.