Dosage Regulation of the Active X Chromosome in Human Triploid Cells 英文参考文献.docVIP

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Dosage Regulation of the Active X Chromosome in Human Triploid Cells 英文参考文献.doc

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Dosage Regulation of the Active X Chromosome in Human Triploid Cells 英文参考文献

DosageRegulationoftheActiveXChromosomein HumanTriploidCells XinxianDeng1,DiKimNguyen1,R.ScottHansen2,3,DanielL.VanDyke4,StanleyM.Gartler2,3, ChristineM.Disteche1,2 * 1Department of Pathology, University of Washington, Seattle, Washington, United States of America, 2Department of Medicine, University of Washington, Seattle, Washington,UnitedStatesofAmerica,3DepartmentofGenomeSciences,UniversityofWashington,Seattle,Washington,UnitedStatesofAmerica,4MayoClinicCollege ofMedicine,Rochester,Minnesota,UnitedStatesofAmerica Abstract Inmammals,dosagecompensationisachievedbydoublingexpressionofX-linkedgenesinbothsexes,togetherwithX inactivation in females. Up-regulation of the active X chromosome may be controlled by DNA sequence–based and/or epigeneticmechanismsthatdoubletheXoutputpotentiallyinresponsetoautosomalfactor(s).TodeterminewhetherX expressionisadjusteddependingonploidy,weusedexpressionarraystocompareX-linkedandautosomalgeneexpression inhumantriploidcells.WhiletheaverageX:autosomeexpressionratiowasabout1innormaldiploidcells,thisratiowas lower(0.81–0.84)intriploidcellswithoneactiveXandhigher(1.32–1.4)intriploidcellswithtwoactiveX’s.Thus,overallX- linked gene expression in triploid cells does not strictly respond to an autosomal factor, nor is it adjusted to achieve a perfect balance. The unbalanced X:autosome expression ratios that we observed could contribute to the abnormal phenotypesassociatedwithtriploidy.Absoluteautosomalexpressionlevelspergenecopyweresimilarintriploidversus diploid cells, indicating no apparent global effect on autosomal expression. In triploid cells with twoactive X’sour data support a basic doubling of X-linked gene expression. However, in triploid cells with a single active X, X-linked gene expressionisadjustedupwardpresumablybyanepigeneticmechanismthatsensestheratiobetweenthenumberofactive Xchromosomesandautosomalsets.Suchamechanismmayactonasubsetofgeneswhoseexpressiondosageinrelation toautosomalexpressionmaybecritical.Indeed,wefoundthatt