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

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Aziz F: C.tl C1lcte Cotu.t ot H1 C4n6 r6Mbn@<br />

ot the HiNF-P/<strong>H4</strong> TF2 interaclion silh <strong>H4</strong>.Sit6 I rogelher with lhe @ncominanl<br />

ahe,alion of the spacing belr€en the M-box and the TATA-box, does ^ot havg<br />

a signilicant eff€cl on <strong>H4</strong> promotff activity (Fig, 29). The simjlarili€s in lhs<br />

.esulls lor lhe liNF P/<strong>H4</strong>TF-2 mutani promolers GT-g and FAIV-14 (Figs. 28,<br />

29) co oborate tiie conclLrson lhat H|NF-P/<strong>H4</strong>TF-2 do€s not contribute<br />

siqnilicanty lo lhe level of <strong>H4</strong> gene transcription when othef Sts ll taclors<br />

rcmair capable oi binding. lvor€over, lh€ ditf€r€nce in spacing ol lho lV- and<br />

TATA-box berween $ese consructs, which could alter possible inreradlons ot<br />

HiNF.M wirh TATA bjnding protein TFtt-O, does nor significanily afiect rh8<br />

olncome ol lhe resulls.<br />

h c$mrasr, the FAM-15/oA1 conslrlcr is expressed ai a 3 lold r€duced<br />

l€v€l rolative lo the wiidtype TM-3/CAT consl.ucl. Th€ lhrce lold reduction in<br />

report€r gene expression obtained wth both INSJo/oAT and FAMn5/CAT<br />

(Figs.3 and 4), whch each repr€s6nl H|NF-M/|BF-2 mltant prornol€rs,<br />

supponsour modelin which th€ HiNF,M/laF-2 inle.acion wilh <strong>H4</strong>-sire llplays<br />

a key roie in determining lhe level ol <strong>H4</strong> transcriplion. In addition, the otfocts<br />

obsetued with the rNs-10 and FAM-15 promoters are quantirively simjlar,<br />

ahhough lhese conslrucrs diller in the spacing wilhin Sile ll and between Siles<br />

I and ll which @dd change sparial intoracrions betwee. F_omorer ladors srill<br />

Taken togelher, ihe s milaril ss n resuts lor GT-g versus FAIV- 1 4 and<br />

INS-10 v€rsus FAlv 15 in three d fier€.r c6l typ€s ars cons slenl wirh th€<br />

concept that difierences in th€ spalial alignmenis oi histone <strong>H4</strong> gen€<br />

129

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