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Experimental Cell Research 246, 11–19 (1999)Article ID excr.1998.4294, available online at http://www.idealibrary.com on

MINIREVIEW

Regulation of Gene Expression by Multiple Forms of TFIIDand Other Novel TAFII-Containing Complexes

Brendan Bell and Laszlo Tora1

Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP,

BP 163, F-67404 Illkirch Cedex, C. U. de Strasbourg, France

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INTRODUCTION

Early work employed in vitro transcription reactionso characterize protein factors required for accurateranscription by RNA polymerase II (Pol II). Chro-atographically separable protein fractions were

ested for their ability to produce correctly initiatedranscripts from promoter DNA fragments [1–3]. Theseifferent chromatographic fractions, which contain dis-inct activities, were shown to be required for basal PolI transcription and designated general Pol II tran-cription factors, TFIIs. After the initial characteriza-ion of these fractions it was shown by using differentootprinting techniques that a factor present in theFIID fractions preferentially binds to the TATA box, aore element shared by many promoters. Subsequentlyt was shown that initiation of the transcription by PolI from a promoter region requires the sequence-spe-ific binding of the TFIID complex to the promoter.inding of TFIID is followed by the subsequent ordered

nteractions of the other basal factors (TFIIA, TFIIB,FIIE, TFIIF, TFIIH, and TFIIJ) and Pol II to yield aroductive preinitiation complex (PIC) [4–6]. Intensefforts to purify the corresponding protein or proteinomplex(es) in the different mammalian TFIID activ-ty-containing fractions to homogeneity were unsuc-essful. A breakthrough came with the discovery that aimilar TATA box binding activity exists in the yeastaccharomyces cerevisiae [7], but that this activityould be isolated as a single polypeptide of 27 kDa [8].his observation set the stage for cloning of yeastATA box binding protein (TBP) [9–11]. The cloning ofhe gene encoding yeast TBP allowed the isolation ofeveral TBP-encoding genes from other eukaryotes [12,3]. The comparison of the size of recombinant TBPith that of mammalian TFIID fractions subsequently

evealed that TFIID, or at least a fraction of the TFIIDctivity, is a tightly associated protein complex com-

1 To whom correspondence and reprint requests should be ad-

Tressed. Fax: (33) 3 88 65 32 01. E-mail: laszlo@igbmc.u-strasbg.fr.

11

osed of TBP and a number (10–13) of TBP-associatedactors (TAFIIs) [13–16]. The discovery that TBP is notnly a component of the TFIID complex, but is alsoresent in transcription complexes functioning in Pol Ind III transcription, placed TBP as a central player inranscription [12, 17]. The fact that recombinant TBPan replace the huge multiprotein complex, TFIID, inasal Pol II transcription reactions in vitro, but that inetazoan cells TBP does not seem to exist alone and is

lways associated with multiprotein complexes, stim-lated much interest in the role of TAFIIs in transcrip-ion regulation. Today most of the TFIID componentsrom S. cerevisiae, Drosophila, and humans have beendentified (Table 1) and partially characterized [16,8–20]. Here we review the roles of TFIID and otherovel TAFII-containing complexes in the regulation oflass II gene expression. We emphasize in particularhose findings that underline the relatively recent ideahat many TAFII-containing complexes, and not a sin-le TFIID, play important roles in transcriptional reg-lation.

TAFII FUNCTIONS

The first clues to TAFII function came from in vitroranscription assays in Drosophila and human systemsn which TFIID, but not TBP, can support activator-ependent transcription. These findings suggestedhat TAFIIs are essential for the response to transcrip-ional activators in vitro [21–27]. Transcriptional acti-ation experiments, using either partially assembledFIID complexes or antibodies raised against TAFIIs,

urther suggested that TAFIIs are required for acti-ated transcription [25–30]. Additional support for thisAFII function comes from studies showing direct andelective interactions between TAFIIs and transactiva-ors [26, 28, 30, 31]. Furthermore, interactions be-ween multiple activators and TAFIIs have been re-orted to result in transcriptional synergy in vitro [32].

hus, TAFIIs may act as specific coactivators in vitro by

0014-4827/99 $30.00Copyright © 1999 by Academic Press

All rights of reproduction in any form reserved.

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12 BELL AND TORA

ngaging in direct and selective interactions withransactivators.

Moreover, in vitro recombinant TBP can substituteor TFIID in reconstituted basal transcription systems,ut does not support transcription from TATA-less pro-oters [23, 33–35]. Although the TAFII–promoter in-

eractions are weaker than the TBP–TATA box inter-ctions, they seem to be critical for transcription fromATA-less promoters. TAFII reported to contact pro-oter DNA include Drosophila (d)TAFII150 [36, 37],

TAFII60 [38], and human (h)TAFIIs 250, 135, 100, 55,6, and 30 (or 31) [39, 40]. Thus, at least some of theAFIIs function to recruit TFIID to TATA-less promot-rs and participate in the promoter recognition surfacef the TFIID complex. TAFIIs might also affect coreromoter function by interacting with other compo-ents of the basal transcriptional machinery [41–43].Evidence showing that TAFIIs can function as coac-

ivators in mammalian cells has come from cell trans-ection experiments, which showed that TAFII28 andAFII135 are required for transcriptional activation byhe nuclear receptors (NRs). Ectopic expression ofhese TAFIIs enhances activation by distinct NRs [44,5]. Expression of TAFII28 also enhances activation byhe viral Tax transactivator, which interacts directlyith TAFII28 and TBP to form a ternary complex [46].urther evidence that TAFIIs may be required for tran-criptional activation in vivo has come from genetictudies in Drosphila melanogaster, which showed thatutations in dTAFII110 lead to specific defects in tran-

criptional activation in Drosophila embryos [47].Surprisingly, recent experiments strongly suggest

hat TAFIIs are not generally required for transcriptionctivation in yeast cells. Depletion or inactivation ofeveral individual yeast TAFIIs does not affect tran-criptional activation by different acidic activators [48,9]. In contrast, depletion of TBP or TFIIB under theame experimental conditions results in a rapid gen-ral decrease of transcription. Nevertheless, TAFIIs dolay an essential role in yeast since mutant strains areot viable. Although several yeast TAFIIs seem not toe generally required for transcriptional activation ineast, they selectively affect the transcription of a sub-et of genes in vivo [49–52]. Thus, TAFIIs seem to playn important role in promoter recognition by interact-ng with the promoter DNA and/or specific componentsf the basal Pol II machinery. In agreement with thisdea, several TAFIIs have been shown to contact differ-nt core promoter elements [37–39] and several TAFIIsave been shown to interact functionally with compo-ents of the basal transcription machinery [42, 43].The observation that cells containing temperature-

ensitive mutations in certain TAFIIs arrest at partic-lar points in the cell cycle upon a shift to the nonper-issive temperature supports the idea that individual

AFIIs may have selective effects on a certain subset of p

enes. Arrest of yTAFII90 and yTAFII150 (Tsm1) mu-ant strains occurs at the G2–M boundary of the cellycle, whereas yTAFII145 mutant strains arrest in G1hase [48, 50]. Interestingly, a hamster cell line con-aining a temperature-sensitive mutation in TAFII250,he hamster homologue of yTAFII145, also undergoes1 arrest upon shifting to the restrictive temperature

53]. Thus, TAFII mutations in higher eukaryotic cellsan also affect a specific subset of genes [54–56]. Theseesults together suggest that TAFIIs may not be gen-rally required for activator-dependent transcription,ut are essential (directly or indirectly) for transcrip-ion of a subset of genes needed, for example, for cellycle progression and that TAFIIs perform specificranscriptional roles. Consistent with the idea thatAFIIs are not generally required for activator-depen-ent transcription, recent experiments suggest thatctivation of transcription can occur with only TBP inither crude HeLa extracts from which the TFIID-ssociated TAFIIs have been depleted [57] or a highlyurified transcription system in the absence of TAFIIs58].

TAFIIs not only interact with promoter DNA and/orther transcription factors but also have enzymaticctivities. Recently it has been shown that TAFII250ossesses an intrinsic kinase activity [59] and alsoistone acetyl transferase (HAT) activity [60–62]. His-one acetylation appears to be an important step in theegulation of transcriptional activity in living cells,ince inactive chromatin seems to be less acetylatedhan active chromatin. The HAT activity of humanAFII250, and its homologues in Drosophila and yeast,

s specific for histone H3 and H4 [62]. However, aurprisingly large number of transcriptional regula-ory proteins possess intrinsic histone acetylase activ-ty; thus it is possible that some of them, for exampleAFII250, acetylate targets other than histones [63,4]. These observations suggest that some of the bio-ogical regulatory properties of TAFIIs may be ascribedo phosphorylation and/or acetylation of cellular pro-eins.

MULTIPLE TFIID COMPLEXES

As more and more antibodies against TBP and theifferent TAFIIs that worked not only in Western blot-ing experiments but also for immunoprecipitationsere developed, it become apparent that there is not

ust a single form of TFIID, but instead multiple TFIIDomplexes exist. Distinct TFIID complexes are com-osed of core TAFIIs which are present in each TFIIDomplex, whereas specific TAFIIs can be found only inFIID subpopulations [18, 19, 24, 26, 65, 66]. By im-unoprecipitating human TFIID complexes from chro-atographically separable fractions that eluted from a

hosphocellulose column (PC) at different salt concen-

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13MULTIPLE TFIID AND OTHER TAFII-CONTAINING COMPLEXES

rations (0.3, 0.5, and 1.0 M KCl), we were able to showhat the different human TFIID complexes exhibitedunctionally distinct properties [24]. Factors associatedith a PC1.0-derived TFIID subpopulation were re-uired in vitro for mediating transcriptional stimula-ion by the activation functions of the estrogen recep-or, VP16, and transcriptional enhancer factor 1 (TEF-), while the PC0.3-derived TFIID subpopulationediated only TEF-1 activation [24]. In an effort to

dentify TAFIIs that confer the differential functions onhe distinct TFIID subpopulations, hTAFII30 was iden-ified from the PC1.0-derived TFIID subpopulation andhown to be present in about 50% of the TFIID com-lexes [26]. In vitro hTAFII30 specifically interactedith the N-terminal part of the E domain of the humanstrogen receptor [26]. This study established that dif-erent classes of activating domains may interact withpecific TAFIIs in functionally distinct TFIID com-lexes.Another human TAFII, hTAFII68, was identified on

he basis of its substoichiometric association with theC1.0-derived TFIID subpopulation [18]. Antibodiesaised against hTAFII68 coimmunoprecipitate a frac-ion of TFIID and, vice versa, anti-TBP or anti-AFII100 mAbs coimmunopurify hTAFII68 [18].TAFII68 shares extensive sequence similarity withhe sarcoma-associated proteins EWS and TLS/FUS67, 68]. Like hTAFII68, TLS/FUS and EWS are alsossociated with distinct TFIID complexes, and TLS/US and EWS seem to be present in TFIID complexesifferent from those containing hTAFII68 [18, 19].WS, TLS/FUS, and hTAFII68 all contain a consensusNA binding domain which allows them to bind notnly RNA, but also single-stranded DNA. Thus, thesepecific TAFIIs may have a role during the preinitiationomplex conversion from a “closed” to an “open” con-ormation or they may participate in defining the pro-

oter selectivity of the distinct TFIID complexes. Al-ernatively, it is possible that these proteins, byinding to the 59 end of the newly synthesized RNA,lay a role in RNA chain initiation and can make aridge between the preinitiation complex formationnd elongation. Consistent with this idea, hTAFII68nd EWS are also associated with the human RNA PolI complex [18, 19]. These findings strongly suggestedhat hTAFII68, TLS/FUS, and EWS play an importantole in the cross-talk between various components ofhe basal transcription machinery.

A unique form of TFIID, termed B-TFIID, has alsoeen described [69]. B-TFIID does not contain the clas-ical core TAFs but instead a single TAF (TAFII170), anTP-dependent inhibitor of TBP-mediated transcrip-

ion [70, 71]. In the above studies multiple forms ofFIID complexes were found in a single human cellype. To this diversity of TFIID complexes another

evel of complexity can be added, namely that cell type- I

pecific TFIID complexes composed of core TAFIIs andell type-specific TAFIIs can also be found. hTAFII105as found uniquely in differentiated human B lympho-

ytes but not in other cell types [72]. The finding thatverexpression of hTAFII105 in B lymphocytes led tohanges in the transcription of some but not all pro-oters tested suggests that cell type-specific TAFIIs

re involved in regulating specific genes that are im-ortant during development and/or in differentiatedissues.

Different forms of TFIID have also been identifiedrom Drosophila and yeast. A distinct dTFIID complexhat contains a number of specific TAFIIs in addition toore dTAFIIs and TBP has been described [66]. Thesepecific dTAFIIs appear to be substoichiometric com-ared to the core dTAFIIs and are thought to direct theromoter selectivity of TFIID during transcription ini-iation [66]. Moreover, both Drosophila and yeastFIID complexes have been identified with and with-ut the corresponding TAFII150 homologue [66, 73], aAFII that was previously shown to play an importantole in binding to core promoter elements [36, 37].hether the human homologue of Drosophila or yeast

AFII150 is a stable component of every human TFIIDomplex or is only present in a subset of TFIID com-lexes needs to be investigated further.Together the above studies highlight the possibility

hat the distinct TFIID complexes have specific roles ini) recognition of different promoters, (ii) interactionith different sets of general transcription factors, and

iii) mediating differential responses to distinct tran-criptional activators. The existence of different TFIIDomplexes is also consistent with the findings thatifferent TAFII mutations only affect a limited specificubset of genes [49, 54–56].

TFIID NOT ONLY NUCLEATES TRANSCRIPTIONINITIATION BY POL II BUT ALSO

INITIATES POLYADENYLATION

Cellular enzymes that cap, splice, and polyadenylateukaryotic pre-mRNAs are targeted in vivo to the nas-ent chains synthesized by Pol II. Placing a mamma-ian Pol II transcription unit under the control of PolII promoter results in a failure to cap, splice, or poly-denylate the transcript [74]. This observation raiseshe question of how the various mRNA-processing en-ymes are recruited to the Pol II transcription initia-ion/elongation complex(es). Unexpectedly, the cleav-ge–polyadenylation specificity factor (CPSF), arotein complex that plays a role in 39 processing ofre-mRNAs by binding the AAUAAA signal sequencend recruiting the other polyadenylation factors [75,6], can stably associate with the TFIID complex [77].he TFIID–CPSF association recruits CPSF to the Pol

I preinitiation complex. After transcription is initiated

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14 BELL AND TORA

nd the carboxy-terminal domain of the largest sub-nit of Pol II is phosphorylated, CPSF dissociates fromFIID and becomes associated with the elongating PolI. Thus, TFIID not only nucleates Pol II transcriptionnitiation, but also initiates the polyadenylation reac-ion by recruiting the CPSF complex to an active pro-oter and, subsequently, via the polymerase, to the

oly(A) site of the nascent RNA [77, 78]. Recruitmentf the polyadenylation “initiation” factor, CPSF, to anctive Pol II promoter via TFIID accounts for Pol IIpecificity of polyadenylation [74]. Thus, TFIID notnly determines the start site of the transcript, but alsoirects the subsequent fate of the 39 end of the mRNA77, 79].

TAFIIS ARE PRESENT IN DISTINCT MULTIPROTEINCOMPLEXES THAT LACK TBP: PARALLELS BETWEENHUMAN TFTC, PCAF, AND YEAST SAGA COMPLEXES

According to their definition, TAFs were thought toxist solely in association with TBP. However, recentlyhe validity of the TAF definition has been seriouslyssaulted since several TAFII-containing multiproteinomplexes have been isolated, either from yeast orrom human cells, which do not contain TBP. Assemblyf the PIC was thought to be nucleated exclusively byhe sequence-specific binding of the TFIID complex tohe different protein coding gene promoters. However,

TAB

TAFII-Contain

Containing TBP

yTFIID dTFIID

AT 145 (130) 230TSM1 150

rich — 110D 40 repeats 90 80

istone H4 like 60 62

67 55istone H3 like 17 (20) 42

25 N.D.istone like 40 30bistone H2B like 68 (61) 30aistone H4 like 19 (FUN81) N.D.

yTBP dTBP

AT — —

Note. The compositions of various TAFII-containing complexes. TBPomplexes are shown on the right. TAFIIs are represented with theroperties of the various TAFIIs are given at the left. Proteins withinTFTC, and hPCAF are from Refs. [84], [35], and [85], respectively.

n vitro transcription experiments demonstrated that [

he cell type-specific Drosophila TBP-related factorTRF) can also mediate polymerase II transcription80]. TRF appears to be associated with a unidentifiedet of proteins, termed nTAFs, distinct from the clas-ical TAFIIs described above. Moreover, a novel multi-rotein complex which does not contain either TBP orBP-like factor, but is composed of a subset of TAFIIs

TAFII135, TAFII100, TAFII80, TAFII55, TAFII31,AFII30, and TAFII20/15) and other proteins, was re-ently isolated from HeLa cells [35]. This novel com-lex, called TBP-free TAFII-containing complexTFTC), is able to replace TFIID both on TATA-con-aining and TATA-less promoters in in vitro transcrip-ion assays. These findings demonstrate that TBP-in-ependent transcription may be much more commonhan originally thought and, thus, may change ournderstanding of the regulation of eukaryotic gene ex-ression. Since TFTC recognizes sequences around thenitiator element on the AdMLP, the TAFIIs present inFTC may play an important role in promoter recog-ition [35]. It is also interesting to note that of the fiveistone fold motive-containing TAFIIs [81, 82] onlyhree are present in TFTC (TAFII80, TAFII31, andAFII20; see also Table 1). The functional data ob-ained with TFTC further demonstrate that TAFIIsave a crucial role not only in recognizing TATA-con-aining and TATA-less promoters, but also in recruit-ng the other general transcription factors into the PIC

1

g Complexes

Lacking TBP

FIID ySAGA hTFTC hPCAF compl.

250 — — —150 — N.D. N.D.135 — 135 —100 90 100 —

(PAF65b)0 (70) 60 80 —

(PAF65a)55 — 55 N.D.

1 (32) 17 (20) 31 (32) 31 (32)30 25 30 3028 — — N.D.

0 (15) 68 (61) 20 (15) 20 (15)18 — — N.D.

TBP — — —

— yGcn5 1 PCAF

ntaining (TFIID) complexes are given on the left and TBP-free TAFII

pparent molecular weights. The HAT activity and some structuralsame horizontal row show homology to each other. Data for ySAGA,

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15MULTIPLE TFIID AND OTHER TAFII-CONTAINING COMPLEXES

ies in TFTC may also play a role in the site-specificinding of TFTC to the promoter and in PIC formation.oreover, among the unidentified proteins a histone

cetyl transferase, other than TAFII250, is likely to beresent since the TFTC complex itself possesses a HATctivity (M. Brand and L.T., submitted for publication).More recently TAFIIs have also been discovered in

wo different histone acetylase complexes: the yeastAGA and the human PCAF complexes [84, 85]. Ini-ially the yeast SAGA complex was described as a.8-MDa adapter/HAT complex that contains the Gcn5istone acetyltransferase and various Ada (Ada1,da2, and Ada3) and Spt (Spt3, Spt7, Spt8, and Spt20)roteins [86]. In addition to these proteins, which haveeen identified by different genetic screens [87–90], theAGA complex also contains a distinct set of yTAFIIs

TAFII90, TAFII68, TAFII60, TAFII25, and TAFII17/20;ee Table 1) but no TBP. The human PCAF complex is

novel multiprotein complex that contains histonecetyl transferase activity. The catalytic subunit of thisomplex is PCAF itself, which is highly homologous touman and yeast Gcn5. The PCAF complex also con-ains the human homologues of Ada2, Ada3, and Spt385]. Furthermore, the PCAF complex contains threereviously identified TAFIIs (TAFII31, TAFII30, andAFII20/15), but not TAFII135, TAFII100, TAFII80,AFII55, TAFII28, TAFII18, or TBP. Although theCAF complex does not contain TAFII100 and TAFII80,

t does contain two highly related proteins, PAF65and PAF65b [85]. In addition to the PCAF complex,uman cells also appear to contain a human Gcn5omplex which has the same polypeptide compositions that of the PCAF complex [85].The TFTC, PCAF, and SAGA complexes share re-arkable similarities (see Table 1): (i) all three com-

lexes have HAT activities (although the TFTC HATemains to be identified), (ii) all of these complexesontain subsets of TAFIIs, (iii) all of these complexesontain only three of the five histone fold motive-con-aining TAFIIs, and (iv) none of these complexes con-ains either TBP or TAFII250. The TFTC and the SAGAomplexes are very similar in respect to their TAFII

omposition, except that the SAGA complex does notontain the yeast homologue of hTAFII135 (since thisAFII does not exist in yeast; see Table 1) or the yeastomologue of TAFII55. The TAFII composition of theuman PCAF complex is somewhat different fromhose of the two other complexes since it has noAFII100 and TAFII80 but rather the related proteins,AF65a and PAF65b, which have never previouslyeen found in TBP-containing (or TFIID) complexes.he PCAF complex contains human versions of theeast Ada2, Ada3, and Spt3 proteins [85]. Homologuesf Ada and Spt proteins are also likely to be present inhe TFTC complex, but they need to be confirmed. It is

nteresting to note that while in the SAGA complex s

here remain only two protein species to be identified,oth the TFTC and the PCAF complexes contain morehan 10 additional polypeptides that have to be iden-ified [35, 84, 85].

In vitro the TFTC complex is able to nucleate PICormation and mediate activation by GAL-VP16 [35];owever, the precise in vivo function of this complexeeds to be further characterized. Genetic studies in-icate that the yeast SAGA complex contains functionshich are involved in promoter-specific transcriptional

ontrol [89–92]. In vitro the SAGA complex seems toromote acetyl-CoA-dependent transcriptional activa-ion from promoter templates occupied by nucleosomes84, 93]. Moreover, the transcriptional activation byAL-VP16 is enhanced by SAGA [93]. However, it hasot been tested whether, similar to TFTC, the SAGAomplex (in the absence of TBP/TFIID) is able to initi-te PIC formation. Apart from the fact that the PCAFomplex acetylates nucleosomes much more efficientlyhan recombinant PCAF, few functional data are avail-ble about this complex.Taking the available functional and structural infor-ation together, it is conceivable that the humanFTC, PCAF, and Gcn5 complexes and the yeast SAGAomplex are all functional homologues. Thus, in theells two different types of TAFII-containing histonecetylase complexes exist: (i) the different TFIID com-lexes which always contain TBP and TAFII145/AFII250 as a catalytic HAT subunit and (ii) the TFTC,CAF, Gcn5, and SAGA complexes which never con-ain TBP and TAFII145/TAFII250 but seem to have acn5/PCAF-type histone acetylase subunit (see Table). Furthermore, TAFII28 and TAFII18 (and their yeastomologues) are not present in the TFTC, PCAF, Gcn5,nd SAGA complexes, while the TFIID complexesever contain Gcn5, Ada, and Spt proteins. The facthat TFTC is able to nucleate initiation of transcriptionuggests that the TFTC/PCAF/SAGA-type complexesnteract directly with promoters and may have also aequence-specific DNA-binding subunit, like TFIID,ut this needs to be confirmed. Thus, while the specificranscriptional roles of TFIID and TFTC/PCAF/SAGA-ype complexes may be different, all these complexeseem to be structurally and functionally more relatedhan originally thought (see Fig. 1). Since most of theon-TAFII components of the SAGA complex are non-ssential yeast genes, it is possible that the TFTC/CAF/SAGA-type complexes play a role in initiationnd activation of transcription at a subset of geneshich are not required under “normal” growth condi-

ions.The realization that TAFIIs are present, not in a

ingle multiprotein unit, but instead as components ofumerous distinct complexes (Fig. 1) is gratifying be-ause it helps to explain observations that previously

eemed paradoxical: (i) the deletion of different TAFIIs

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17MULTIPLE TFIID AND OTHER TAFII-CONTAINING COMPLEXES

n yeast does not have a global effect on transcription,ii) the deletion of different yeast TAFIIs results inistinct phenotypes, and (iii) TAFIIs can play roles inifferent aspects of gene regulation, from the regula-ion of cell-cycle-specific genes to tissue-specific tran-cription of genes to core promoter selectivity. Theiscovery of distinct TFIID complexes, together withhe revelation that TAFIIs are present in other TBP-ree complexes, adds another level of complexity to ournderstanding of the regulation of protein-coding genexpression (see Fig. 1). The exciting challenge that lieshead is to decipher how the incorporation of TAFIIsnto functionally distinct complexes orchestrates theiriverse biochemical roles, including promoter recogni-ion, transcriptional activation, cell cycle progression,istone acetylation, alteration of chromatin structure,nd polyadenylation. One thing is clear: further bio-hemical and genetic experiments with TAFII mutantshich selectively affect the function of TFIID or TFTC/CAF/SAGA-type complexes in yeast or mammalianells will be needed to fully elucidate the cellularvents mediated by TAFIIs.

The authors are very grateful to M. Brand, J.-C. Dantonel, D.irschner, A.-C. Lavigne, and F. J. Dilworth, for critically reading

he manuscript, and apologize to colleagues whose work could beited only indirectly in this review. The present work was supportedy grants from the CNRS, the INSERM, the Hopital Universitaire detrasbourg, the Ministere de la Recherche et Technologie, The Fon-ation pour la Recherche Medicale, and the Association pour laecherche contre le Cancer.

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2. Matsui, T., Segall, J., Weil, P. A., and Roeder, R. G. (1980).Multiple factors required for accurate initiation of transcriptionby purified RNA polymerase II. J. Biol. Chem. 255, 192–196.

3. Davison, B. L., Egly, J. M., Mulvihill, E. R., and Chambon, P.(1983). Formation of stable preinitiation complexes betweeneukaryotic class B transcription factors and promoter se-quences. Nature 301, 680–686.

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eceived August 20, 1998