Developmental Biology | |
Differences in Krox20-Dependent Regulation of Hoxa2 and Hoxb2 during Hindbrain Development | |
Miguel Manzanares1  Heather Marshall1  Robb Krumlauf1  Stefan Nonchev1  Mark K Maconochie1  | |
[1] Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom | |
关键词: Krox20; Hoxa2; Hoxb2; hindbrain segmentation; rhombomeres; transgenic mice; pattern formation; vertebrate evolution; gene regulation; | |
DOI : 10.1006/dbio.2001.0197 | |
学科分类:生物科学(综合) | |
来源: Academic Press | |
【 摘 要 】
Duringhindbraindevelopment,segmentalregulationoftheparalogousHoxa2andHoxb2genesinrhombomeres(r)3and5involvesKrox20-dependentenhancersthathavebeenconservedduringtheduplicationofthevertebrateHoxclustersfromacommonancestor.ExaminingtheseevolutionarilyrelatedcontrolregionscouldprovideimportantinsightintothedegreetowhichthebasicKrox20-dependentmechanisms,cis-regulatorycomponents,andtheirorganizationhavebeenconserved.TowardthisgoalwehaveperformedadetailedfunctionalanalysisofamouseHoxa2enhancercapableofdirectingreporterexpressioninr3andr5.Thecombinedactivitiesoffiveseparatecis-regions,inadditiontotheconservedKrox20bindingsites,areinvolvedinmediatingenhancerfunction.ACTTT(BoxA)motifadjacenttotheKrox20bindingsitesisimportantforr3/r5activity.TheBoxAmotifissimilartoone(Box1)foundintheHoxb2enhancerandindicatesthatthecloseproximityoftheseBoxmotifstoKrox20sitesisacommonfeatureofKrox20targetsinvivo.Twootherrhombomericelements(RE1andRE3)areessentialforr3/r5activityandsharecommonTCTmotifs,indicatingthattheyinteractwithasimilarcofactor(s).TCTmotifsarealsofoundintheHoxb2enhancer,suggestingthattheymaybeanothercommonfeatureofKrox20-dependentcontrolregions.ThetworemainingHoxa2cis-elements,RE2andRE4,arenotconservedintheHoxb2enhanceranddefinedifferencesinsomeofcomponentsthatcancontributetotheKrox20-dependentactivitiesoftheseenhancers.Furthermore,analysisofregulatoryactivitiesoftheseenhancersinaKrox20mutantbackgroundhasuncovereddifferencesintheirdegreeofdependenceuponKrox20forsegmentalexpression.Together,thisworkhasrevealedasurprisingdegreeofcomplexityinthenumberofcis-elementsandregulatorycomponentsthatcontributetosegmentalexpressionmediatedbyKrox20andshedslightonthediversityandevolutionofKrox20targetsitesandHoxregulatoryelementsinvertebrates.
【 授权许可】
Unknown
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