Page 1 \ ?^p 6r.1 CELL CYCLE CONTROL OF HUMAN H4 ...
Page 1 \ ?^p 6r.1 CELL CYCLE CONTROL OF HUMAN H4 ...
Page 1 \ ?^p 6r.1 CELL CYCLE CONTROL OF HUMAN H4 ...
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i.leraclion elem€nt, sil6 ll, Thr€€ ssqu€nce-sP6cilic lr.n:icriplion tactors<br />
inr€r€ci wirh ovB.lapping recognition motib whhin sit€ ll: HiNF M, which is<br />
idenlicarto interieron .egulalory facior lRF.2, the <strong>H4</strong> subtyp€_specilic protein<br />
HiNF,P/<strong>H4</strong>TF-2, as well as the muili-Protsin comPl6x HiNF_D whlch conialns<br />
fie cul/homeodomain protein coP-1, coc2, cyclin A and an BB ielated<br />
protein, To addr€ss the p.6cise contribulion ot th€ rocognilion €lements tor<br />
each ol these tacrors to $e level ot <strong>H4</strong> gene lranscription, we pedormed a<br />
sysr€maric mutalional analyses ol sir6 ll transcri ional molifs. The resultinq<br />
site ll promot6r mutsn$ w€re l€sled tor ability ro bind each ol lh€ sn€ ll<br />
coqnate pror€ins. and subs€qu€ntly tundionsny 6v6lualed for ability to conrer<br />
<strong>H4</strong> ranscriprional adivny using cttimeic <strong>H4</strong> promot€/cAf fusion cooslrucls.<br />
Resulls show that the recognition sequdnce ol HiNF.lM/lFF-2 ls ths dominant<br />
componenr aid modulares <strong>H4</strong> gene t ans.rpron bvsls bi 3lold. Howeve.,<br />
lhe mllripre overapping rocognition sequences tor HiNFM, -P and 'o<br />
togethe. modulate <strong>H4</strong> gene transcription levels by at least an order ol<br />
magnirude c€rr cycr€ analyses reveals rhd mutalims ol lhe IRF-2, HiNF-P and<br />
HiNF-D bndng sil€s, eilher separale o. in combinallon. have diflerent eflBcls<br />
on <strong>H4</strong> gene transcription du nq lhe csll cycle. Ihus, it is proposed lhat the<br />
p.oper lemporal contol of <strong>H4</strong> g€na transc.iption duing the c6llcycrs roquires<br />
lhe integrated activities ol mulrrpls trans€riPtion lactors at a composile c€ll<br />
cycle fegularory domain, <strong>H4</strong>'site ll. This composhe organizalion supports<br />
respo.slveness to muliiple c€llsiqnalling paihways moduLatinq lhe acliviuBs ol<br />
<strong>H4</strong> qene ranscription lactoE du.ing the c6ll crcl6 to accommodale r€qure_<br />
menis jor erpresslon in cells and llssuos with uniqus phenolyprc prcpedies
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