A歉下l G k糕嚣Chi neseSc／enceBv#eti n2004 Vol49N o 8574—578Coacti vatorCBP／p300i ncreased theacti vi tyofC／EBP．m edi ated hum ani nterl euki n- 5gene prom oterLIUChunyan‘SH AOYangguang＆H U AN G Bai qu，LUJ un+，LI Li n，TANJ i ang，Insti tuteofG eneti csandCyt ol ogy，N ort heastN orm alU ni versi ty，Changchun 130024，Chi na+Theauthors contri butedequal l yto thi s w orkCorrespondenceshoul d be addressed toH uangBai qu( e—m ath huangbq@nenueducn)Abst racttype-2 Thel per( Th2) cel l s，pl aysan essenti al rol e i n the de-vel opm ent of al l ergi c di seases，such as al l ergi c asthm a．H i s-toneaeetyl transf eraseacetyl ati nghi stones，resul ti ngi nopenstructure of ehrom ati nand acti vetranscri pti on．Adenovi ri l l S protei nE1Ai nhi bi ts theacti vi ty of CBP，D300．Inthi sst udy, w e anal yzedthe effects ofE1A on IL．5 geneprom oter／l ucfferase reporter acti vi ty．Theresul ts show ed that E1A protei n i nhi bl ted the acti vi tyPM A／i onom yci n-sti m ul atedreporterconstruct．In contrast．overexpressi onCBP／p300- bi ndi ng def ecti ve E1A A2- 36protei n di d nothi bi tIL一5gene prom oter acti vi ty．Thesedata dem onstratedf or the fi rst ti m e that transcri pti onal coacti vator CBP／p300w as i nvol ved i n the acti vati on of IL- 5 gene prom oter．E1Aprotei n can m odul ate CBP／p300 f uncti on0fIL一5壮nepl asm i d．Furtherm ore，i n col l aborati on w i th transcri pti onfactorC／EBP．CBP／p300m oter／l uci ferasereporterexpressi on．Thi sf urtheri nsi ght i nt0 the m echani sm s of transcri pti onall ati on of IL- 5gene．Interl euki n．5( IL-5) ，expressed pri m ari l ybyCBP／p300rem odel schrom ati nbyofIL．5geneprom oter／l uci feraseofthei n-to acti vatethetranscri pti onprom oter／l uei ferasereporteracti vatedIL一5genepro-study provi desregu·Keyw ords：CBP／p300，IL-5，C／EBP[ j ，EtA，H ATH um ani nterl euki n一5(IL· 5)i s ahi ghl y speci fi c cyto—ki neproduced byvol ved i ncontrol l i ngtheproducti on，di fferenti ati on，andacti vati on of eosi nophi l s【11m aj or cause of ti ssuedam ageasthm aandotheral l ergi cstrongl y i m pl i catedas a m ai or factor control l i ng the l ocali nfi l trati on and acti vati on of eosi nophi l s i n asthm aIL一5i sproducedT—l ym phocytes，fol l ow i ngacti vati on w i thanti genstogens—Thi s acti vati on can be m i m i cked by sti m ul ati onw i th phorbel12-m uri state 13一acetate( PM A) andcal ci umi onophoresbody‘ 1IL一5 expressi on can al so be i nduced i nT．hel percel l s by treatm ent w i mIL一2 or IL一15“ J ．Li ke m ost cyto一 万方数据acti vated Tl ym phocytes，andi si n—21Increase ofeosi nophi l si sresul ti ngi n thesym ptom sofdi seases吼IL一5ahasbeenpri m ari l ybyacti va把dor m i —or l i gati on of the CD 3co—receptorw i th anti —al574ki ne genes．the regul ati on of IL一5 j s ful fi Il ed pri m ari l y atthe l evel of transcri pti onand i s l i kel y to be control l ed．to al arge extent，by regul atory el em entsgi onthatgenem entsthatactasprotei n bi ndi ngC／EBPl 3 bi nds fouri ncreasesIL一5gene transcri pti on byi nteracti on to一235regi onof theprom oter∞J ．G ATA．bi ndi ng protei nand AP一1are requi redto regul atethe IL一5expressi on—Ets protei nsi n the regul ati on of the IL．5 expressi on i nTh2l ym phocytes【l ? ．The di rect connecti on betw een chrom ati nrem odel i ngand transcri pti onal acti vati on has been i ncreasi ngl y dem -onstrated i n recent yearsChrom ati n rem odel i ngvi a hi s-tonem odi f yi ng enzym es，nam el yhi stoneacetyl transferase( H AT) and hi stonedeacetyl ase( H D AC) ，i si nvol ved i ntranscri pti onalIt has been proposedthat acetyl ati on of the￡一am i nogroupof l ysi neresi dues at theN H 2- term i naldom ai n of hi stoncsprom otesdestabi l i zati on ofthenucl eosom e．resul ti ngi n i ncreasedaccessi bi l i tyof theopen chrom ati n to thetranscri pti onalhi stonedeacetyl asereverses thi sprocess by rem ovi ngtheacetylgroups，and repressesw i th thi s hypothesi s．severalri chm ent ofhyperacetyl ated hi stones w i thi n the transcri p—ti onal l y acti ve chrom ati n i n vi vo，and hypoacetyl ated hi s—tones w ere show n to be concentrated i n transcnptl O na儿vsi l enced dom ai nsl ¨ 1 Thetranscri pti onal coacti vators CBPori gi nal l yi denti fi edasaspeci fi cki nase—i nduci bl e dom ai n of CREB，and the hi ghl y rel atedprotei n p300．cl oned throughi ts i nteracti on w i th adenovi ．rus protei n E1A．have10ng been recogni zed as key m ol e—cul esforgene regul ati onby com m uni cati ngtranscri pti on factorsand the basalcry【J 31．It has been characteri zed thatCBP／p300has H ATacti vi ty and can acetyl ate nucl eosom aI hi stones andm anytranscri pti onfactors The adenovi ral protei nE1A has beenshow nto i nhi bi t CBP／p300 acti vi ty” “ ．CBP／p300ubi qui tousl y expressed，gl obalthat has cri ti calrol es i n a w i de vari ety of cel l ul ar proc—esses，i ncl udi ngeel lcycl eCBP／p300 provi desabri dge di rectl y i nteracti ngboth w i th a w i devari etyoftranscri pti onfactors and w i tl lcom ponents of the basaltranscri pti on m achi nery, i ncl ud—i ng TBP．TFIIB．TFIIE and TFIIF” ? ．CBP／p300can al soserve the functi on ofa seaffbl d．thereby bri ngi ng togetheravari etyof di fferentprotei ns．CBP／p300sti m ul ates tran—scri pti onofspeci fi c genes by i nteracti ng，ei ther di rectl ythrough cofactors，w i th num erous prom oter—bi ndi ngscri pti on factors?，i ncl udi ng Cm BPD，p53，G ATA．1andN F．KBt9，16一一W e show i n thi s arti cl e that adenovi rali nhi bi ted IL- 5gene prom oteri n the prom oteracti vi tyof there-can i nfi uence thetranscri pti onalIL一5gene prom otercontai nsm ul ti pl e responseel e·si tes．Fori nstance．si teson the IL．5gene prom oterandare i m portantacti vati on andrepressi on。respecti vel y? 】hi stone—D N A i nteracti oni nm achi nery，w hi l etranscri pti onstudi es dem onstrated the an—Inagreem entprotei n bi ndi ngthebetw eentranscri pti on m achi n．i satranscri pti onalcoacti vatorcontrol ，di fi erenti ati onandapoptosi sortran．protei nE1AThi si nhi bi ti onacti vi tyChi nese Sci enceBul l eti nVoI49N o 6M arch2004
