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

I
azz F Con CYb Cnror ot H4 G@e ntns.ldion
cell cycLe enhanc€d transc ption al the G1/S lransiton Thus, at app€ars that
HiNF-M/|RF-2 is analogous to oTF-1/ocTn which pedorms a simil* dual
lunction in cel cycle regulalion ol human histone H2B transc ption (Flelcher el
a/.,1987).
Ou rcsulls also rcpr€s€nt the li.sl direct indication that natural
sequ€nc€ vaiation in the 5 regions ol dislinct H4 96n€s
has lunctional
consequences lor lh€ exent to which human H4 promoteE are aciive This
observation is rolevanl to the overall expression ol hislono H4 genes' bocauss
hi$one H4 proleins are lranslaled trom mLrltiple mFNAs encodlng very smilal
or idernicsl proteins and tunclional H4 mRNAs are lranscribed lrom distincl H4
genes displaying considerable variation in |he organizallon ol s' ilanking
sequences. This promoter heterogeneity is .eflect€d by ditierences in lhe
presence, number ol copies, relalive location spacing' and orientaton or
consensus ta.scriptional elemenls. Forexample, the sit6llregion olih€ H4_A
gene and rhe H4 (FO1O8) gene dille. al seve.al kev nucleotides .esulting in
absenc€ of bindlng sites lor HINF-!|/IRF_2 and HiNF-O (COC2/cvcln A/RB'
related complex) in the H4.A gene. oirect jncorporation oi one set ol
nucleotide !€riations (mutant INS'10) inthe promoler ol lhe H4 {FO108) gene
results in a 3 iold decrease in the evel oi lranscripton The posslblity arises
thal diilerenl H4 P.omole. organizaiions may have evolved to accomodale
deleopmenta and homeostalc responsive.ess ro a brcad spectlm ol
slgnaling pathways that med ate competency
r65
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prolleral on and ce I cycle