Mechanics and Dynamics of X-Chromosome Pairing at X Inactivation 英文参考文献.docVIP

MechanicsandDynamicsofX-ChromosomePairingatX Inactivation AntonioScialdone1,2,MarioNicodemi2,3 * 1Dipartimento diScienzeFisiche, Universita` diNapoli‘‘Federico II’’,Naples,Italy, 2INFN,Naples,Italy, 3Department ofPhysicsandComplexityScience,Universityof Warwick,Coventry,UnitedKingdom Abstract AttheonsetofX-chromosomeinactivation,thevitalprocesswherebyfemalemammaliancellsequalizeXproductswith respect to males, the X chromosomes are colocalized along their Xic (X-inactivation center) regions. The mechanism inducing recognition and pairing of the X’s remains, though, elusive. Starting from recent discoveries on the molecular factors and on the DNA sequences (the so-called ‘‘pairing sites’’) involved, we dissect the mechanical basis of Xic colocalization by using a statistical physics model. We show that soluble DNA-specific binding molecules, such as those experimentally identified, can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomesbutonlywhentheirconcentration,orchemicalaffinity,risesaboveathresholdvalueasaconsequenceofa thermodynamicphasetransition.Wederivethelikelihoodofpairinganditsprobabilitydistribution.Chromosomedynamics has two stages: an initial independent Brownian diffusion followed, after a characteristic time scale, by recognition and pairing. Finally, we investigate the effects of DNA deletion/insertions in the region of pairing sites and compare model predictionstoavailableexperimentaldata. Citation:ScialdoneA,NicodemiM(2008)MechanicsandDynamicsofX-ChromosomePairingatXInactivation.PLoSComputBiol4(12):e1000244.doi:10.1371/ journal.pcbi.1000244 Editor:GaryD.Stormo,WashingtonUniversity,UnitedStatesofAmerica ReceivedJune2,2008;AcceptedNovember6,2008;PublishedDecember26,2008 Copyright:?2008Scialdone,Nicodemi.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited