SHREC复合物通过乙酰化调节着丝粒内H3核小体和Cnp1核小体的替换.pdfVIP

Abstract

Correctassemblyofcentromeresisoneofthebasicrequirementsforcell

division.CENP-A/Cnp1nucleosomeslocatedspecificallyinthecentromerecore

regionarethebasisforkinetochoreassemblyandplayakeyroleinchromosome

segregationduringmitosisandmeiosis.Inthisproject,weusedageneticscreening

systeminSchizosaccharomycespombetofindthegenesinvolvedincentromere

assembly,andrevealedanewmechanismforquantitativeregulationofCENP-A/

Cnp1nucleosomeincorporationincentromere.Previousstudieshaveshownthatthe

MBFtranscriptionfactorcomplexregulatesthelevelofofCENP-A/Cnp1

nucleosomeincorporationthroughmodulatingcnp1transcriptionlevel.Inthisstudy,

wefoundthat:(1)besidestranscriptionalregulation,Dnajc9regulatesthelocalization

ofCnp1nucleosomeandplaysanimportantroleinmaintainingtheboundaries

betweentheCnp1-domain/centralregionandthepericentromericheterochromatin

regions.TheSHRECcomplex–containingClr1,Clr2,andClr3-alsoaffectsthe

localizationofCnp1nucleosomeatanon-transcriptionallevel,anditsmechanismis

differentfromthatofDnajc9.(2)ThedeacetylationfunctionoftheHDACmodulein

SHRECreversesthelocalizationofCnp1nucleosome.Thisfunctionmayspecifically

targetthecentromerecentralregionviaClr2,inwhichtheD10siteofClr2playsan

importantrole.(3)AcetylationofH3K14inthecentromericregionsupportsH3

expulsionandhelpsCnp1nucleosomeincorporationintothecentromericcoreregion.

However,notallH3K14ac-relatedproteins,suchasSir2,actoncentromericcore

regiontoregulatethelocalizationofCnp1.