真核生物启动子数据库

302–303NucleicAcidsResearch,2000,Vol.28,No.12000OxfordUniversityPress

TheEukaryoticPromoterDatabase(EPD)

RouaïdaCavinPérier,VivianePraz,ThomasJunier,ClaudeBonnardandPhilippBucher*

SwissInstituteofBioinformaticsandSwissInstituteforExperimentalCancerResearch,Ch.desBoveresses155,1066-Epalingess/Lausanne,Switzerland

ReceivedOctober6,1999;AcceptedOctober8,1999

ABSTRACT

TheEukaryoticPromoterDatabase(EPD)isananno-tatednon-redundantcollectionofeukaryoticPOLIIpromotersforwhichthetranscriptionstartsitehasbeendeterminedexperimentally.Accesstopromotersequencesisprovidedbypointerstopositionsinnucleotidesequenceentries.Theannotationpartofanentryincludesadescriptionoftheinitiationsitemappingdata,exhaustivecross-referencestotheEMBLnucleotidesequencedatabase,SWISS-PROT,TRANSFACandotherdatabases,aswellasbiblio-graphicreferences.EPDisstructuredinawaythatfacilitatesdynamicextractionofbiologicallymean-ingfulpromotersubsetsforcomparativesequenceanalysis.WWW-basedinterfaceshavebeendevel-opedthatenabletheusertoviewEPDentriesindifferentformats,toselectandextractpromotersequencesaccordingtoavarietyofcriteria,andtonavigatetorelateddatabasesexploitingdifferentcross-references.TheEPDwebsitealsofeaturesyearlyupdatedbasefrequencymatricesformajoreukaryoticpromoterelements.EPDcanbeaccessedathttp://www.epd.isb-sib.chDATABASEDESCRIPTION

Thetermpromoterhastwodifferentmeaningsinbiology:(i)ageneregionimmediatelyupstreamofatranscriptioninitiationsite,and(ii)acis-actinggeneticelementcontrollingtherateoftranscriptioninitiationofagene.TheEukaryoticPromoterDatabase(EPD)isadatabaseofpromotersintheformersense.InformationaboutpromotersinthelattersensecanbefoundinotherdatabasessuchasTRANSFAC(1),ooTFD(2),TRRD(3),PlantCARE(4)andPLACE(5).

EPDwasoriginallydesignedasaresourceforcomparativesequenceanalysisand,assuch,hasplayedaninstrumentalroleinthecharacterizationofeukaryotictranscriptioncontrolelements(6,7),aswellasinthedevelopmentofeukaryoticpromoterpredictionalgorithms(8).Themainpurposeofthedatabaseistokeeptrackofexperimentaldatathatdefinetranscriptioninitiationsitesofeukaryoticgenes.Thistypeoffunctionalinformationislinkedtopromotersequencesviamachine-readablepointerstopositionswithinsequencesoftheEMBLnucleotidesequencedatabase(9).

EPDisarigorouslyselected,curatedandquality-controlleddatabase.Inordertobeincluded,apromotermustfulfillanumberofconditionslaiddownintheusermanual.Mostimportantly,thetranscriptionstartsitemustbemappedexperimentallywithanestimatedprecisionof 5bporhigher.AllinformationinEPDoriginatesfromacriticalexaminationandindependentinterpretationoftheexperimentaldatapresentedinthecitedresearchpublications.PublishedconclusionsandfeaturetableannotationsinEMBLentriesareneverblindlyreliedupon.Atpresent,EPDisconfinedtopromotersrecognizedbytheRNAPOLIIsystemofhighereukaryotes(multicellularplantsandanimals).Notethatthisrestrictiondoesnotaprioriexcludeviralpromoters.

EPDisalsoastrictlynon-redundantdatabase.Thegeneralruleisthatoneentrycorrespondstoonetranscriptioninitiationsiteinagenome.Organismsaredistinguishedatthetaxonomiclevelofthespecies.Accordingtothispolicy,datafromdifferentliteraturesourcespertainingtothesametranscriptioninitiationsitesarerepresentedbythesameentry.Likewise,promotersbelongingtodifferentallelesofthesamegene,ortothesamegeneindifferentsubspecies,arecoveredbythesameentryregardlessofwhethertheydifferinsequence.Theusermanualprovidesmoredetailsabouthowcertainnon-trivialcasessuchaspromotersoftandemlyrepeatedgenesorretro-transposableelements,arehandled.

AcomprehensivedescriptionofthecontentsandformatofEPDhasbeenpublishedearlier(10).Userinterfacesandsoftwaresupportforlocalinstallationshavebeenpreviouslydescribed(11).

RECENTDEVELOPMENTSDatabase

Theobjectiveofexhaustivecross-referencingbetweenEPDpromotersandEMBLsequencesisbeinggivenhighpriorityatthemoment,especiallywithregardtogenomesthatarecomplete(Caenorhabditiselegans)oratanadvancedstageofsequencing(Arabidopsis,Drosophila,human).Asaconsequence,thenumberofEMBLcross-referenceshasincreasedby>1000sincelastyear(Table1).Moreover,theinternalEPDcross-referenceshavebeenrevised.Untilnow,suchlinkswereonlyusedtoconnectalternativepromotersofthesamegene.Infuturereleases,promotersofdifferentgenesoccurringatashortdistancefromeachother(

*Towhomcorrespondenceshouldbeaddressed.Tel:+[1**********];Fax:+[1**********];Email:[email protected]

hasbeenintroducedandsofarbeenpopulatedwithkeywordsimportedfromSWISS-PROT(12).Thisfeatureisintendedtoenhancethequerycapabilitiesofvariousaccesstools.Additionalkeywordsrelatingtopropertiesofthepromoterratherthantopropertiesofthecorrespondinggeneproductwillbeaddedinthenearfuture.

Table1.Databasecross-referencesinEPDrelease60DatabaseNumberoflinksEPDinternal188EMBL(9)2978TRANSFAC(1)1700SWISS-PROT(12)1058FlyBase(16)116MIM(17)234MGD(18)126MEDLINE

2393

Documentation

Theusermanualhasbeenextensivelyrevised.Bibliographicreferenceshavebeenaddedtothesectionexplainingtherepresentationoftranscriptmappingdata.Someofthemareaccompaniedbydirecthyperlinkstofiguresinonlinejournalsexemplifyingaparticulartechnique.Severaladditionaldocumentshaverecentlybeenmadeavailableovertheweb.Onecontainsalistofall‘homologygroups’definedinEPD.Suchgroupsconsistofhomologouspromotersexhibitingsignificantsequencesimilarityinthe–79to+20regionamongthemselves.Anotherdocumentpresentsthehierarchicalpromoterclassifi-cationsystemofEPD.

Promoterelementdescriptions

Weightmatrixdescriptionsoffourmajoreukaryoticpromoterelements(TATA-box,initiator,GC-boxandCCAAT-box)havepreviouslybeenderivedfromEPDrelease17(7).WehavenowdecidedtomakeupdatedversionsofsuchmatricesavailableonayearlybasisfromtheEPDwebpages.ThelatestversionswereproducedfromEPDrelease60usingaBaum–WelchhiddenMarkovmodeltrainingalgorithm(programbuildmodelofSAMrelease1.3.3,Hughey&Krogh1998,http://www.cse.ucsc.edu/research/compbio/sam.html).ACCESSFTP

Thefollowingfilesareavailablefromftp.epd.isb-sib.ch/pub/databases/epd

•Flat-filescontainingtheEPDdatabaseinthenewandintheoldformat.

•EPDusermanual.

•SequencelibrariesinEMBLandFASTAformatcontainingpromotersequencesfrom–499to+100relativetothetran-scriptionstartsite.

•AslightlyreducedversionofEPDinASN.1formatdesignedforimportintotheGenBank–Entrezdataenvironment(13),includingaformaldatadescriptioninASN1.

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•IcarusscriptsforindexingEPDbySRS(14).WWW

Thefollowingservicesareofferedathttp://www.epd.isb-sib.ch•AccesstoEPDentriesbyIDoraccessionnumber.Thefollowingformatsareavailable:textonly,HTMLandHTMLcombinedwithagraphicrepresentationofsequenceobjectsbyaJavaapplet(15).

•ApagefordownloadingpromotersequencesubsetsdefinedinEPD.

•AccesstoEPDentriesandcorrespondingpromotersequencesviaaqueryform.

AccesstoEPDviaSRSisprovidedbytheSwissEMBNetnodeathttp://www.ch.embnet.org/SUPPLEMENTARYMATERIAL

RelevantURLlinksareavailableatNAROnline.ACKNOWLEDGEMENT

EPDisfundedinpartbygrant31-54782.98fromtheSwissNationalScienceFoundation.REFERENCES

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