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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a2i2 F cdt c$t. connd d <strong>H4</strong> Gm Tdnscionon<br />
proximar promorer r€gions ol rhe human <strong>H4</strong>-Fo108 (Paurier at,, 1987) and H3-<br />
sT519 (Paul er a/., 19ag) histone gsnes wi|h genomic oNasel tootprinung<br />
assays (using solatBd nlcei) and g€nomc oMs tingeFdnling assays (lsins<br />
i.ract celrs). ao|h 9en6s appear to hav€ two protein/DNA interacrion domains,<br />
desiqnared <strong>H4</strong>-sire I, <strong>H4</strong>-sire rr, Hlsir6 | .nd H3-sn6 rr, r6spediv€1y. These<br />
domaids rep.ese c.ucial cis acling cortrol elements, and are lo.ated wilhin<br />
the lnst 0.2 kb lpslfeam of lhe coding region. The number ol pfotein/ONA<br />
co.iacts at glanlne.esdles detecled wilhin these stes is consisrent with<br />
each doman infer.cling wth more than one ONA binding prc\en in vivo. A<br />
major local poinr ol rhe studies prese €d here is related to lhe lunctionar<br />
cha.acterization of rhe tacrors binding ro <strong>H4</strong>-sit€ lr.<br />
Transcriplional modsls ror hlston€ gan€ 169ulatlon<br />
ar rh6 ons6r or rhis srudy (JUy 1992), rhe initiar concgpts for<br />
lnderstanding huhan histone <strong>H4</strong> gene l.ansc.iprion had bo€n eslabllshed<br />
(sreinera/, 1994iHdntz, r99liOstey 6ta/., 1991). The study d€scib€d 'n<br />
this thesis rep.es€nts an elpansion ol previous studies on histone gene<br />
regllarion (A.J. van wijnen, 1991, Ph.D. rh€sis, Departmenr ot c6ll Bioogy,<br />
unNersiry ol lvassachuserts, 19s1: A.L. Famsey-Ewing, Ph.o. thesis,<br />
Oepadmed ol hmunoloqy and M€dic€l Microbiology, Universily ol Flo.ida,<br />
1991). h rhese srudies, seral <strong>H4</strong>.sir6 lr rranscndio. taclors we.e<br />
characterized, and s€veral nucleotides implicatsd in cell cycle contro! were<br />
ldentiied (s6€ F gs. 3, 4 a.d 5). How6v6r, limitod intormallon was avallable on<br />
the specitic conrriburions of <strong>H4</strong>-sr€ ll bnding protsins to <strong>H4</strong> gene<br />
22
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