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Page 1 \ ?^p 6r.1 CELL CYCLE CONTROL OF HUMAN H4 ...

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aj| F. Cdt Cttt. C@ud ot H1 cetu rnnsu,p!,@<br />

It was furrher €xamined rhat lhe signficance ol reductions in rc/rg<br />

ratos lor the CAT rnFNAsignats obse.ved with 1wo ot the mutant<strong>H4</strong> promotsr<br />

constucls. Full scale cel cycte synchfonjes with tour difierenr c6I linss wef6<br />

perlomed (Figs. 3740) lo address whether reduclions in lhe redued T3/m<br />

fanos ar€ r€Lated to changes in the maqniiude ot hision€ gene irascipnon<br />

during ea y s phase, or wherher this ratio r€lects a shft in lhe timing oi rh6<br />

peak ol <strong>H4</strong> prcnoter aclivity to tor exampta eartier or tster me-points, The<br />

RNas6 prot€crion assays show that CAT mRNA tevets diven by r're I!,tSp-16<br />

mltant<strong>H4</strong> promor€r,which can not bind HiNF-M/|FF2. ar€ vory simitar to CAT<br />

mnNAlevels obssrved lor lho witdryp€ <strong>H4</strong> promoter FO1O8 celline (Figs.37<br />

and 38). In com€st, mutant suBrl which is not capabt€ ot bindtng HiNF-D,<br />

appears t0 display a modesl delay in the riming of maamat <strong>H4</strong> promoier<br />

adlvity (Fig. 38). Fu.rhermore, rhe muiani MprMrT consruq appears ro navs<br />

a smilar limlnq in lhe peak ol rnaxlrnat tansc.ipton, but dspays pantaL<br />

retention ol cell qde dependent etevations in <strong>H4</strong> gene ransc.iplton (Fig,4O),<br />

ll is concluded that cell cycle conl.ol represents a comptex mechanism which<br />

nvolr'es s-bne co_Lbu0ons oimurripl€di nct pror€,ns<br />

1!i

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