Cell Cycle–Specified Fluctuation of Nucleosome Occupancy at Gene Promoters 英文参考文献.docVIP

CellCycle–SpecifiedFluctuation ofNucleosomeOccupancy atGenePromoters Gregory J.Hogan, Cheol-Koo Lee¤,Jason D.Lieb* DepartmentofBiologyandCarolinaCenterforGenomeSciences,UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica ThepackagingofDNAintonucleosomesinfluencestheaccessibilityofunderlyingregulatoryinformation.Nucleosome occupancy and positioning are best characterized in the budding yeast Saccharomyces cerevisiae, albeit in asynchronous cell populations or on individual promoters such as PHO5 and GAL1–10. Using FAIRE (formaldehyde- assisted isolation of regulatory elements) and whole-genome microarrays, we examined changes in nucleosome occupancy throughout the mitotic cell cycle in synchronized populations of S. cerevisiae. Perhaps surprisingly, nucleosome occupancy did not exhibit large, global variation between cell cycle phases. However, nucleosome occupancyatthepromotersofcellcycle–regulatedgeneswasreducedspecificallyatthecellcyclephaseinwhichthat geneexhibitedpeakexpression,withthenotableexceptionofS-phasegenes.WepresentdatathatestablishFAIREas a high-throughput method for assaying nucleosome occupancy. For the first time in any system, nucleosome occupancywasmappedgenome-widethroughoutthecellcycle.Fluctuationofnucleosomeoccupancyatpromotersof mostcellcycle–regulatedgenesprovidesindependentevidencethatperiodicexpressionofthesegenesiscontrolled mainlyattheleveloftranscription.ThepromotersofG2/Mgenesaredistinguishedfromothercellcyclepromotersby an unusually low baseline nucleosome occupancy throughout the cell cycle. This observation, coupled with the maintenance throughout the cell cycle of the stereotypic nucleosome occupancy states between coding and non- codingloci,suggeststhatthelargestcomponentofvariationinnucleosomeoccupancyis‘‘hardwired,’’perhapsatthe levelofDNAsequence. Citation:HoganGJ,LeeCK,LiebJD(2006)Cellcycle–specifiedfluctuationofnucleosomeoccupancyatgenepromoters.PLoSGenet2(9):e158.DOI:10.1371/journal.pgen.