Bridging the Resolution Gap in Structural Modeling of 3D Genome Organization 英文参考文献.docVIP

Review BridgingtheResolutionGapinStructuralModelingof3D GenomeOrganization MarcA.Marti-Renom1*,LeonidA.Mirny2 1StructuralGenomicsLaboratory,BioinformaticsandGenomicsDepartment,CentrodeInvestigacio′nPr?′ncipeFelipe,Valencia,Spain,2Harvard-MITDivisionofHealth SciencesandTechnology,andDepartmentofPhysics,MassachusettsInstituteofTechnology,Cambridge,Massachusetts,UnitedStatesofAmerica physicalandbiological)thatexplainexperimentalobservations;(ii) the second approach aims at integrating diverse experimental Abstract: Over the last decade, and especially after the advent of fluorescent in situ hybridization imaging and chromosome conformation capture methods, the avail- abilityofexperimentaldataongenomethree-dimensional observations into a system of spatial restraints to be satisfied, thereby constraining possible structural models of the chromatin. Thegoalofbothapproachesisdual:toobtainmostaccurate3D organization has dramatically increased. We now have and 4D representation of chromatin architecture and to under- access to unprecedented details of how genomes standphysicalconstraintsandbiologicalphenomenathatdetermine organize within the interphase nucleus. Development of itsorganization.Theseapproachesarereminiscentoftheprotein- newcomputationalapproachestoleveragethisdatahas already resulted in the first three-dimensional structures of genomic domains and genomes. Such approaches folding field where the first strategy was used for characterizing protein‘‘foldability’’andthesecondwasimplementedformodeling expand our knowledge of the chromatin folding princi- ples, which has been classically studied using polymer physicsandmolecularsimulations.Ouroutlookdescribes computational approaches for integrating experimental data with polymer physics, thereby bridging the resolu- tion gap for structural determination of genomes and genomicdomains. the structure of proteins using nuclear magnetic resonance and other experimental constraints. In fact, our outlook consistently r