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

AzzF cett Crct. ContolatH4Gen ldn*tipttan
abe(ant histone syd$esis. Therelore, is not slrictly necsssary to i.voks
negative regulalory transcription lactors io ordsr to strlng€ntly conl.ol histono
oornrogualion ol histone gen6 tanscriPtion as measu.€d bv reporter
genes has been obserued du.ing muine hepalic development .etlecting lhs
onset ol in v,!o qui€scen@ and ditlercn0ation (van wijnen el a/., 1991). These
modilications in lranscrlption colr€spond lo similar d€cr€ases ln histon€
mBNA levels, This ind cates lhattfafscrlplonalregulation is a primary mod€ ot
gene control dLring developmeni, Becaus€ transcriplion rales may or€ciy
corelate wilh the presence ot ralo-limiing kansacting lactors, lhese nndings
provide a i rst ind cal on for cell grofih relaled, developrnenla reguallon of
hisrone gerj6 transcr ptron ractors
Hisrone g€ne tanscription control by cls-.egulatory eremenrs
This laboratory has been involved lor a long iime in the study ol rhe
regLrlation oi hlstone gene expression th.ougholt th€ cell cycle oi cullLrred
human cels.The h stone gene rspfes€.lan €xc€ll€nt modsl ior the study ol
rumorogenesis or the genes which do€s not express inaLly h dlfferentaled
state, bln rather lurned on and otl in a t'm6 dependent lashion. The frst 20o
basepans upslream of fte histon€ Protein codi.g sequence has been
desgnaled as lho proxlmal promoter, and sequences beyond that as he
dista promotor ALthough lhsr€ is svidenc6 suggesllng lhat dislal y ocaled
promoter elements are capable oi inllu€ncing rhe levol ol hisbne g€oe
exprcssion (Krc€ge! er a/., 19a4, hese pulative distal regulatory eEmenls ar€
20