Modeling DNA Sequence-Based cis-Regulatory Gene Networks

Developmental Biology

Eric H. Davidson¹  Hamid Bolouri¹ 

[1] Science & Technology Research Centre, University of Hertfordshire, Hatfield, Hertfordshire, AL10 9AB, United Kingdom

关键词: gene regulatory network;    model;    endo16 gene;    regulatory genomics;   

DOI  :  10.1006/dbio.2002.0617

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Genenetworkanalysisrequirescomputationallybasedmodelswhichrepresentthefunctionalarchitectureofregulatoryinteractions,andwhichprovidedirectlytestablepredictions.Thetypeofmodelthatisusefulisconstrainedbytheparticularfeaturesofdevelopmentallyactivecis-regulatorysystems.Thesesystemsfunctionbyprocessingdiverseregulatoryinputs,generatingnovelregulatoryoutputs.Acomputationalmodelwhichexplicitlyaccommodatesthisbasicconceptwasdevelopedearlierforthecis-regulatorysystemoftheendo16geneoftheseaurchin.Thismodelrepresentsthegeneticallymandatedlogicfunctionsthatthesystemexecutes,butalsoshowshowtime-varyingkineticinputsareprocessedindifferentcircumstancesintoparticularkineticoutputs.Thesamebasicdesignfeaturescanbeutilizedtoconstructmodelsthatconnectthelargenumberofcis-regulatoryelementsconstitutingdevelopmentalgenenetworks.Theultimateaimofthenetworkmodelsdiscussedhereistorepresenttheregulatoryrelationshipsamongthegenomiccontrolsystemsofthegenesinthenetwork,andtostatetheirfunctionalmeaning.Thetargetsitesequencesofthecis-regulatoryelementsofthesegenesconstitutethephysicalbasisofthenetworkarchitecture.Usefulmodelsfordevelopmentalregulatorynetworksmustrepresentthegeneticlogicbywhichthesystemoperates,butmustalsobecapableofexplainingtherealtimedynamicsofcis-regulatoryresponseaskineticinputandoutputdatabecomeavailable.Mostimportantly,however,suchmodelsmustdisplayinadirectandtransparentmannerfundamentalnetworkdesignfeaturessuchasintra-andintercellularfeedbackcircuitry;thesourcesofparallelinputsintoeachcis-regulatoryelement;genebatteryorganization;anduseofrepressivespatialinputsinspecificationandboundaryformation.Successfulnetworkmodelsleadtodirecttestsofkeyarchitecturalfeaturesbytargetedcis-regulatoryanalysis.

【 授权许可】

Unknown