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

Mz F: C.ll Crcl. Cotuat at H4 Gere faNdo an
mediate binding of HiNF-r',4, -P and -D together arc capablo ormodurating H4
gene ransiplion by an order ol m6gnitude.
The HiNF-P/H4-TF2 btnding mo{finlh6 H4 gene t3
dlspensabls tor H4 gene promo!€r actlvlty/, vtvo
Located inthe mlddle oi H4-SI€ llis a NGGTCCGNN mori, (Fig. s) that
represenrs the most highly cons6d6d sequenc€ in hislone H4 genes. For
examplei this conserved eleme is locaied in bo$ lh6 human H4,FO108
gene, aswelasttu analogous humanH4-A gene characl€rlzed byHelnrz and
colleagues. Cross-competition assays have shown rhat borh genes intefact
wirh HiNF-P/H4-TF2, bur only th3 H4,FO1OA gene appears ro interacr
addilionally wirh HiNF-M/|RF-2 and HiNF-D_ Ihs NGGTccGNN,motit
comprises thB main clusrer of m€thylation intedercnce motifs ior HINF,
P/H4TF-2, and $e ntegity ol lhis recognition motit is €ssenlial ior HiNF-
Abfogalion ot rhe NGGTCCGNN,moTIf by substirr.rtion oI th€ I
nucleo d€s cornprlsing rlris motif (mut6 GI.g), aborlshes H NF,P/H4-TF-2
binding to lhe mutant GI-g promoter, blr has no eiteci on rhe lnteractions of
H|NF-M/|FF2 or HiNF-O with H4,Sit€ tl (Frg. 25)- Functional activiry ol ths
mulanl GT 9 promoter is comparabl6 ro ihar of rh€ wildtype TM,3 promot€r
(F9. 28). Th!s, inlegrlty or the highly conserued NGCTCCGNN motil, and
recogniuon by ils cognate lactor HiNF-P/H4TF-2, is dspensable lor hiqh tevel
kanscriprion ol lhe H4,Fo10a gen6 when olher transcri ional morils in sit€ I
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