Genes and function最新文献

{"title":"Genomes.","authors":"L. Wolpert","doi":"10.1163/9789004387584_009","DOIUrl":"https://doi.org/10.1163/9789004387584_009","url":null,"abstract":"In the last decade, the rise of affordable high-throughput sequencing technologies has led to rapid advances across the biological sciences. At the time of writing, annotated reference genomes are available within most clades of eukaryotic pathogens, and including un-annotated sequences over 550 genomes are available in total. This has greatly facilitated studies in many areas of parasitology. In addition, the volume of functional genomics data, including analysis of differential transcription and DNA-protein interactions, has increased exponentially. With this unprecedented increase in publicly available data, tools to search and compare datasets are also becoming ever more important. A number of database resources are available, and access to these has become fundamental for a majority of research groups. This chapter discusses the current state of genomics research for Author Affiliations: 1 Department of Biology, University of Pennsylvania, Philadelphia USA Email: oharb@upenn.edu Tel: +1 215-746-7019. 2 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA Email: ucb@sanger.ac.uk. 3 Wellcome Trust Centre for Molecular Parasitology, B6-28 SGDB, 120 University Place, Glasgow, G12 8TA Email: kathryn.crouch@glasgow.ac.uk Tel: +44 141 330 3746. 4 University of Maryland School of Medicine, Insti-tute for Genome Sciences, BioPark II, Room 645, 801 W. Baltimore St., Baltimore, MD 21201 USA JS Email: jcsilva@som.umaryland.edu OI Email: KAbolude@som.umaryland.edu KT Email: KTretina@som.umaryland.edu Tel: +1 410-706-6721. 5 Institute of Integrative Biology, University of Liv-erpool, Liverpool, L69 7ZB, UK Email: F.SilvaFranco@liverpool.ac.uk. 6 Department of Cell and Molecular Biology, Uppsala University, BMC, Box 596, SE-75123, Uppsala, Sweden Email: staffan.svard@icm.uu.se Tel: +46 184714558. 7 Vector Biology Department, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Email: gareth.weedall@lstmed.ac.uk. Corresponding author. This is an Accepted Manuscript of a book chapter published by Springer-Verlag Wien in Molecular Parasitology: Protozoan Parasites and their Molecules, available online: https://www.springer.com/gp/book/9783709114155. © Springer-Verlag Wien 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free f","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1 1","pages":"3-4"},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47361479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular heterogeneity of regulatory elements of the mouse GATA-1 gene","authors":"Antonella Ronchi,&nbsp;Marco Cirò,&nbsp;Linda Cairns,&nbsp;Luca Basilico,&nbsp;Paola Corbella,&nbsp;Paola Ricciardi-Castagnoli,&nbsp;Michael Cross,&nbsp;Jacques Ghysdael,&nbsp;Sergio Ottolenghi","doi":"10.1046/j.1365-4624.1997.00021.x","DOIUrl":"10.1046/j.1365-4624.1997.00021.x","url":null,"abstract":"<p>The GATA-1 gene encodes a transcription factor expressed in early multipotent haemopoietic progenitors, in more mature cells of the erythroid, megakaryocytic and other lineages, but not in late myeloid precursors; its function is essential for the normal development of the erythroid and megakaryocytic system. To define regulatory elements of the mouse GATA-1 gene, we mapped DNaseI-hypersensitive sites in nuclei of erythroid and haemopoietic progenitor cells. Five sites were detected. The two upstream sites, site 1 and site 2, represent a new and a previously defined erythroid enhancer respectively. The site 1 enhancer activity depends both on a GATA-binding site (also footprinted <i>in vivo</i>) and on several sites capable of binding relatively ubiquitous factors. A DNA fragment encompassing site 1, placed upstream of a GATA-1 minimal promoter, is able to drive expression of a simian virus 40 (SV40) T-antigen in the yolk sac, but not bone-marrow cells, obtained from mice transgenic for this construct, allowing <i>in vitro</i> establishment of immortalized yolk-sac cells. A similar construct including site 2, instead of site 1, and previously shown to be able to immortalize adult marrow cells is not significantly active in yolk-sac cells. Sites 4 and 5, located in the first large intron, have no enhancer activity; they include a long array of potential Ets-binding sites. <i>Mnl</i>I restriction sites, overlapping some of the Ets sites, are highly accessible, in intact nuclei, to <i>Mnl</i>I. Although these sites are present in all GATA-1-expressing cells studied, they are the only strong sites detectable in FDCP-mix multipotent progenitor cells, most of which do not yet express GATA-1. The data indicate that appropriate GATA-1 regulation may require the co-operation of different regulatory elements acting at different stages of development and cell differentiation.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 4","pages":"245-258"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00021.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomes","authors":"Lewis Wolpert","doi":"10.1046/j.1365-4624.1997.00005.x","DOIUrl":"10.1046/j.1365-4624.1997.00005.x","url":null,"abstract":"","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"3-4"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00005.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The level of the tissue-specific factor GATA-1 affects the cell-cycle machinery","authors":"David Whyatt,&nbsp;Alar Karis,&nbsp;Inge Harkes,&nbsp;Anton Verkerk,&nbsp;Nynke Gillemans,&nbsp;Andrew Elefanty,&nbsp;Gino Vairo,&nbsp;Rob Ploemacher,&nbsp;Frank Grosveld,&nbsp;Sjaak Philipsen","doi":"10.1046/j.1365-4624.1997.00003.x","DOIUrl":"10.1046/j.1365-4624.1997.00003.x","url":null,"abstract":"<p>GATA-1 is a tissue-specific DNA-binding protein containing two zinc-finger-like domains. It is expressed predominantly in erythrocytes. Consensus binding sites for GATA-1 have been found in the regulatory elements of all erythroid-specific genes examined. GATA-1 protein is required for erythroid differentiation beyond the proerythroblast stage. In this paper, we demonstrate that the overexpression of GATA-1 in murine erythroleukaemia (MEL) cells alleviates DMSO-induced terminal erythroid differentiation. Hence, there is no induction of globin gene transcription and the cells do not arrest in the G1 phase of the cell cycle. Furthermore, we demonstrate that expression of GATA-1 in non-transformed erythroid precursors also affects their proliferative capacity and terminal differentiation, as assayed by adult globin gene transcription. To gain insight into the mechanism of this effect, we studied the levels and activities of regulators of cell-cycle progression during DMSO-induced differentiation. A decrease in cyclin D-dependent kinase activity was observed during the induction of both control and GATA-1-overexpressing MEL cells. However, cyclin E-dependent kinase activity decreased more than 20-fold in control but less than 2-fold in GATA-1-overexpressing MEL cells upon induction. Thus GATA-1 may exert its effects by regulating cyclin E-dependent kinase activity. We also show that GATA-1 binds to the retinoblastoma protein <i>in vitro</i>, but not to the related protein p107, which may indicate that GATA-1 interacts directly with specific members of the cell-cycle machinery <i>in vivo</i>. We conclude that GATA-1 regulates cell fate, in terms of differentiation or proliferation, by affecting the cell-cycle apparatus.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"11-24"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00003.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the renin–angiotensin system in a congenic renin Dahl salt-sensitive rat","authors":"Nicholas DiPaola,&nbsp;John Rapp,&nbsp;Paul Brand,&nbsp;William Beierwaltes,&nbsp;Patricia Metting,&nbsp;Steven Britton","doi":"10.1046/j.1365-4624.1997.00017.x","DOIUrl":"10.1046/j.1365-4624.1997.00017.x","url":null,"abstract":"<p>When an ∼30 centiMorgan (cM) region of chromosome 13 containing the renin gene from the Dahl salt-resistant rat (R) was introgressed into the Dahl salt-sensitive rat (S), the resulting congenic rat (designated S.R<i>-Ren</i>) had a systolic blood pressure on a 2% (w/w) salt diet that was 24 mmHg lower than that of its S counterpart. Due to the large size of the transferred segment (over 30 million bp), the question remained as to whether or not the renin gene was the cause of the blood-pressure difference between the strains. We evaluated the role of the renin–angiotensin system in S.R<i>-Ren</i> and S rats fed a 0.05% salt diet by examining differences between strains in (1) expression of renin in three tissue types, (2) the blood-pressure response to blockade of both angiotensin-converting enzyme and angiotensin II receptors, and (3) pressure natriuresis. No differences were found in renin levels in plasma, kidney or adrenal gland between strains. The blood-pressure responses to the angiotensin-converting-enzyme inhibitor captopril and to the angiotensin II-receptor blocker saralasin in conscious S and S.R<i>-Ren</i> rats were similar. Furthermore, renal function, evaluated by a pressure-natriuresis index that took into account both the time and the arterial pressure needed to excrete an acute salt load, did not differ between strains. Our findings therefore fail to demonstrate a role for the renin gene in conferring lower blood pressure in the congenic rat and suggest that there is an unknown arterial-pressure-regulating locus in this 30 cM region of chromosome 13.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 3","pages":"215-226"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00017.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-expression screens in vertebrate embryos: more than meets the eye","authors":"Christof Niehrs","doi":"10.1046/j.1365-4624.1997.00022.x","DOIUrl":"10.1046/j.1365-4624.1997.00022.x","url":null,"abstract":"","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 4","pages":"229-231"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00022.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20596714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and molecular characterization of murine GATA-1 in Aspergillus defines a critical role for the N-terminal finger","authors":"Mark Caddick,&nbsp;David Peters,&nbsp;Paul Hooley,&nbsp;Andrew Nayler","doi":"10.1046/j.1365-4624.1997.00002.x","DOIUrl":"10.1046/j.1365-4624.1997.00002.x","url":null,"abstract":"<p>We have utilized <i>Aspergillus nidulans</i> as a model system for the characterization of the major vertebrate transcription factor GATA-1. This has been achieved both by analysing the function of murine GATA-1 directly and by using direct gene replacement to introduce chimaeric <i>areA::GATA-1 </i>derivatives at the <i>areA </i>locus<i>,</i> which encodes a GATA factor involved in regulating nitrogen metabolism in <i>A. nidulans</i>. Although GATA-1 shows only limited function when expressed in <i>A. nidulans</i>, the C-terminal GATA DNA-binding domain can replace the native GATA domain of AREA and retain near wild-type function. Surprisingly, inclusion of the N-terminal DNA-binding domain of GATA-1 has a major role in determining the function of <i>areA::GATA</i> constructs <i>in vivo</i>, leading to a general loss of activation. This negative function is partially dominant and is dependent on both the fidelity of the zinc-chelating structure and a second factor encoded by <i>A. nidulans.</i> The presence of two GATA domains also disrupts modulation of AREA activity. The ability of duplicate GATA domains to disrupt normal signal transduction is not dependent on the relative position of the domains or on the fidelity of the zinc-chelating structure. This demonstrates the utility of nitrogen metabolism’s regulation in <i>A. nidulans </i>as a model system for the molecular and genetic characterization of heterologous GATA factors while also providing insights into native <i>Aspergillus </i>regulatory components.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 1","pages":"37-49"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00002.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transcriptional regulatory strategy of the rat tissue kallikrein gene family","authors":"Evert Kroon,&nbsp;Raymond MacDonald,&nbsp;Robert Hammer","doi":"10.1046/j.1365-4624.1997.00027.x","DOIUrl":"10.1046/j.1365-4624.1997.00027.x","url":null,"abstract":"<p>We have analysed the transcriptional regulatory strategy of the rat tissue kallikrein gene family, a strategy that provides universal submandibular gland expression of all family members coupled with otherwise disparate expression of individual members in a wide variety of organs. To test whether a locus control region (LCR) or individual gene enhancers control the family, the expression patterns of rat kallikrein genes were examined in transgenic mice bearing a series of rat genomic fragments spanning the kallikrein locus. Each fragment, present in recombinant P1 phage clones, contained two or three linked members of the rat family. Rat (<i>r</i>) genes <i>KLK1</i>, <i>KLK2</i>, <i>KLK3</i>, <i>KLK7</i>, <i>KLK8</i>, <i>KLK9</i> and <i>KLK10</i> on four different P1 clones were all correctly expressed at high levels in the submandibular glands of transgenic mice and in general showed the correct extra-salivary patterns characteristic of each family member. Moreover, when the neighbouring family members <i>rKLK1</i> and <i>rKLK3</i> were separated on non-overlapping fragments and tested in mice, each transgene was expressed correctly in the submandibular gland and in other organs characteristic of that gene. Thus the family locus is not controlled by an LCR; rather each gene appears to have an associated transcriptional enhancer that specifies high submandibular expression and contributes to the additional organ specificity of the family member.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 5","pages":"309-319"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00027.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26610203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mammalian homologue of the Drosophila retinal degeneration B gene: implications for the evolution of phototransduction mechanisms","authors":"Francesca Rubboli,&nbsp;Alessandro Bulfone,&nbsp;Silvia Bogni,&nbsp;Anna Marchitiello,&nbsp;Massimo Zollo,&nbsp;Giuseppe Borsani,&nbsp;Andrea Ballabio,&nbsp;Sandro Banfi","doi":"10.1046/j.1365-4624.1997.00015.x","DOIUrl":"10.1046/j.1365-4624.1997.00015.x","url":null,"abstract":"<p>Comparative analysis of homologous genes in distantly related species provides important insights into the evolution of complex physiological processes. The <i>Drosophila retinal degeneration B</i> (<i>rdgB</i>) gene encodes a protein involved in phototransduction in the fly. We have isolated a human gene, <i>DRES9</i>, and its murine homologue (<i>Dres9</i>), which show a high degree of similarity to the <i>Drosophila rdgB</i> gene. RNA <i>in situ</i> hybridization studies performed on mouse-embryo tissue sections at various developmental stages revealed that <i>Dres9</i> is expressed at very high levels in the neural retina and in the central nervous system (CNS), similar to its <i>Drosophila</i> counterpart. The high level of sequence conservation and similarities in the expression patterns of <i>rdgB</i> and <i>DRES9</i> during development in <i>Drosophila</i> and mammals indicate that Dres9 is the orthologue of RdgB, and strongly suggest a possible functional conservation of these proteins during evolution. <i>DRES9</i> encodes a phosphatidylinositol-transfer protein, suggesting that phosphatidylinositol may have a role as an intracellular messenger in vertebrate phototransduction. The identification of this gene and the study of its expression pattern in mammals will help shed new light on the evolution of vision mechanisms and suggest <i>DRES9</i> as a candidate gene for human retinopathies.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 3","pages":"205-213"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00015.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20597863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An auxiliary peptide required for the function of two activation domains in upstream stimulatory factor 2 (USF2) transcription factor","authors":"Laurence Gourdon,&nbsp;Anne-Marie Lefrançois-Martinez,&nbsp;Benoît Viollet,&nbsp;Antoine Martinez,&nbsp;Axel Kahn,&nbsp;Michel Raymondjean","doi":"10.1046/j.1365-4624.1997.00014.x","DOIUrl":"10.1046/j.1365-4624.1997.00014.x","url":null,"abstract":"<p>Ubiquitous upstream stimulatory factors (USF1, USF2a and USF2b) are members of the basic-helix–loop–helix-leucine-zipper family of transcription factors that have been shown to be involved in the transcriptional response of the L-type pyruvate kinase (L-PK) gene to glucose. To understand the mechanisms of action of the USF2 isoforms, we initiated a series of co-transfection assays with deletion mutants and Gal4–USF2 fusions. The transactivating efficiency of the different native and mutant factors was determined at similar DNA binding activity. We found that: (i) exons 3- and 5-encoded regions are activation domains, (ii) a modulator domain encoded by exon 4 could be necessary to their additive action, (iii) a hexapeptide encoded by the first 5′ codons of exon 6 is indispensable for transmitting activation due to both exon 3- and exon 5-encoded domains to the transcriptional machinery. Therefore, USF2 presents a modular structure and mediates transcriptional activation thanks to two non-autonomous activation domains dependent on an auxiliary peptide for expressing their activating potential.</p>","PeriodicalId":79601,"journal":{"name":"Genes and function","volume":"1 2","pages":"87-97"},"PeriodicalIF":0.0,"publicationDate":"2008-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1046/j.1365-4624.1997.00014.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20598001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}