High Mobility Group Protein 1 Interacts Specifically with the Core Domain of Human TATA Box-binding Protein and Interferes with Transcription Factor IIB within the Pre-initiation Complex

Abstract

The high mobility group (HMG) box domain has defined a family of proteins, mostly transcription factors, that specifically interacts with DNA on the minor groove and sharply bends it. The founding member of the family, HMG1, does not specifically recognize regular B-DNA but is recruited to DNA by interaction with other transcription factors and TATA box-binding protein (TBP). However, conflicting effects of HMG1 on transcription have been reported. We show that the interaction between HMG1 and TBP is species-specific. This interaction in turn affects the interaction of TBP with transcription factor (TF) IIB and is competed by TFIIA. A primary binding site was mapped to the H2′ α-helix in the highly conserved core domain of human TBP. On HMG1, the primary binding site was only in the HMG box A, and HMG box A was also sufficient to interact with native TFIID. Both HMG boxes efficiently repressed transcription in vitro as fusions to the Gal4-DNA binding domain. Additionally, HMG box B showed a weak level of activation at very low amounts. These results suggest a general involvement of HMG1 at the early stages of polymerase II transcription that may result in subtle activation or repression of individual genes. The high mobility group (HMG) box domain has defined a family of proteins, mostly transcription factors, that specifically interacts with DNA on the minor groove and sharply bends it. The founding member of the family, HMG1, does not specifically recognize regular B-DNA but is recruited to DNA by interaction with other transcription factors and TATA box-binding protein (TBP). However, conflicting effects of HMG1 on transcription have been reported. We show that the interaction between HMG1 and TBP is species-specific. This interaction in turn affects the interaction of TBP with transcription factor (TF) IIB and is competed by TFIIA. A primary binding site was mapped to the H2′ α-helix in the highly conserved core domain of human TBP. On HMG1, the primary binding site was only in the HMG box A, and HMG box A was also sufficient to interact with native TFIID. Both HMG boxes efficiently repressed transcription in vitro as fusions to the Gal4-DNA binding domain. Additionally, HMG box B showed a weak level of activation at very low amounts. These results suggest a general involvement of HMG1 at the early stages of polymerase II transcription that may result in subtle activation or repression of individual genes. High mobility group protein 1 (HMG1) 1The abbreviations used are: HMG1, high mobility group protein 1; cisplatin, cis-diamminedichloroplatinum; EMSA, electrophoretic mobility shift assay; FPLC, fast protein liquid chromatography; pol, polymerase; PIC, pre-initiation complex; GST, glutathione S-transferase; TBP, TATA box-binding protein; hTBP, human TBP; hcTBP, human core TBP; yTBP, yeast TBP; ycTBP, yeast core TBP; WT, wild type; TF, transcription factor; TAF, TBP-associated factor. is an abundant, highly conserved nuclear protein found in practically all eukaryotes. It is structured in three domains, one C-terminal highly acidic domain and two basic domains, A and B. The structures of the A and B domains have been solved in solution by NMR (1Hardman C.H. Broadhurst R.W. Raine A.R.C. Grasser K.D. Thomas J.O. Laue E.D. Biochemistry. 1995; 34: 16596-16607Crossref PubMed Scopus (166) Google Scholar, 2Read C.M. Cary P.D. Crane-Robinson C. Driscoll P.C. Norman D.G. Nucleic Acids Res. 1993; 21: 3427-3436Crossref PubMed Scopus (246) Google Scholar). Both domains adopt a very similar L-shaped structure, formed by two short and one long α-helix, that is known as the HMG box domain. An increasing number of proteins containing one or more HMG box domains have been described; the HMG box domains for which the structure has been solved, such as the ones in LEF-1 or SRY, are very similar to the HMG box domains of HMG1 (3Love J.J. Li X. Case D.A. Giese K. Grosschedl R. Wright P.E. Nature. 1995; 376: 791-795Crossref PubMed Scopus (521) Google Scholar, 4Werner M.H. Huth J.R. Gronenborn A.M. Clore G.M. Cell. 1995; 81: 705-714Abstract Full Text PDF PubMed Scopus (433) Google Scholar). However, whereas SRY and LEF-1 interact with DNA in the minor groove with a certain sequence specificity, HMG1 (and the related protein HMG2) does not interact specifically with regular B-DNA. Nevertheless, HMG1 shows a clear preference for binding angled structures in the DNA without any sequence specificity, such as cisplatin-modified DNA, bulged DNA, or four-way DNA junctions (5Bianchi M.E. Beltrame M. Paonessa G. Science. 1989; 243: 1056-1059Crossref PubMed Scopus (554) Google Scholar, 6Locker D. Decoville M. Maurizot J.C. Bianchi M.E. Leng M. J. Mol. Biol. 1995; 246: 243-247Crossref PubMed Scopus (48) Google Scholar). Structure-specific DNA recognition has also been observed for the HMG box domains of several other proteins such as UBF and SRY (7Ferrari S. Harley V.R. Pontiggia A. Goodfellow P.N. Lovell-Badge R. Bianchi M.E. EMBO J. 1992; 11: 4497-4506Crossref PubMed Scopus (382) Google Scholar, 8Pöhler J.R.G. Norman D.G. Bramham J. Bianchi M.E. Lilley D.M.J. EMBO J. 1998; 17: 817-826Crossref PubMed Scopus (103) Google Scholar). The HMG boxes of HMG1 are also a place for protein-protein interactions. Both HMG1 domains A and B have been reported to interact with the POU domains of Oct2 and HOXD9 (9Zappavigna V. Falciola L. Citterich M.H. Mavilio F. Bianchi M.E. EMBO J. 1996; 15: 4981-4991Crossref PubMed Scopus (217) Google Scholar, 10Zwilling S. König H. Wirth T. EMBO J. 1995; 14: 1198-1208Crossref PubMed Scopus (218) Google Scholar), and full-length HMG1 has been shown to interact with TBP (11Ge H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google Scholar) and recently with p53 (12Jayaraman L. Moorthy N.C. Murthy K.G.K. Manley J.L. Bustin M. Prives C. Genes Dev. 1998; 12: 462-472Crossref PubMed Scopus (284) Google Scholar) and steroid hormone receptors (13Boonyaratanakornkit V. Melvin V. Prendergast P. Altmann M. Ronfani L. Bianchi M.E. Taraseviciene L. Nordeen S.K. Allegretto E.A. Edwards D.P. Mol. Cell. Biol. 1998; 18: 4471-4487Crossref PubMed Scopus (306) Google Scholar). The fact that many members of the HMG box family are transcription factors (14Bianchi M.E. Lilley D.M.J. DNA-Protein: Structural Interactions. Oxford University Press, Oxford1994: 177-200Google Scholar), along with the interactions of HMG1/2 with several transcription factors, has suggested a role for HMG1/2 in transcription. In this respect, enhancement of progesterone receptor binding to specific DNA sequences (15Oñate S.A. Prendergast P. Wagner J.P. Nissen M. Reeves R. Pettijohn D.E. Edwards D.P. Mol. Cell. Biol. 1994; 14: 3376-3391Crossref PubMed Google Scholar), reversible repression of basal and activated transcription in vitro (11Ge H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google Scholar, 16Stelzer G. Goppelt A. Lottspeich F. Meisterernst M. Mol. Cell. Biol. 1994; 14: 4712-4721Crossref PubMed Scopus (55) Google Scholar), and co-stimulation of activated transcription both in vitro andin vivo (9Zappavigna V. Falciola L. Citterich M.H. Mavilio F. Bianchi M.E. EMBO J. 1996; 15: 4981-4991Crossref PubMed Scopus (217) Google Scholar, 10Zwilling S. König H. Wirth T. EMBO J. 1995; 14: 1198-1208Crossref PubMed Scopus (218) Google Scholar, 17Ogawa Y. Aizawa S. Shirakawa H. Yoshida M. J. Biol. Chem. 1995; 270: 9272-9280Crossref PubMed Scopus (55) Google Scholar, 18Shykind B.M. Kim J. Sharp P.A. Genes Dev. 1995; 9: 1354-1365Crossref PubMed Scopus (130) Google Scholar) have been well documented. Here we describe a remarkably species-specific interaction of HMG1 with human TBP that affects the interaction of TFIIB with hTBP and is competed by TFIIA. The interaction takes place between the highly conserved core domain of hTBP and the HMG1 box A domain; HMG box A also interacts with the high molecular mass TFIID complex in crude nuclear extracts. HMG box A represses transcription in vitro on its own, and this activity can be significantly increased by using Gal4-binding domain fusions. Plasmids pT7-HMG1bA and pT7-HMG1bB, expressing rat HMG1 boxes A and B, respectively, have already been described (19Bianchi M.E. Falciola L. Ferrari S. Lilley D.M.J. EMBO J. 1992; 11: 1055-1063Crossref PubMed Scopus (215) Google Scholar). pET14b-HMG1 was constructed by inserting anNdeI-BamHI insert from pT7-HMG1 (20Bianchi M.E. Gene (Amst.). 1991; 104: 271-275Crossref PubMed Scopus (34) Google Scholar) in pET14b (Novagen). An internal NdeI site at position +44 in HMG1 was previously mutated without affecting the amino acidic sequence. Constructs expressing His6-tagged human and yeast TBP were provided by A. Hoffmann and R. Roeder (The Rockefeller University, New York) and J.-M. Egly (Institut de Génétique, Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France), respectively. The human TFIIB expression plasmid was obtained from D. Reinberg (Robert Wood Johnson Medical School, University of Medicine and Dentistry, Piscataway, NJ). pGST-HMG1box A was constructed by inserting aNcoI-EcoO109 (Klenow-filled) fragment from pET14b-HMG1 into pGEX-KG digested with HindIII (Klenow-filled) and NcoI. pGST-HMG1box B was constructed by inserting an NdeI (Klenow-filled)-HindIII fragment obtained from pT7-HMG1bB into a pGEX-KG digested withSmaI and pGEX-KG is a of with an A was obtained by the sequence to domain A, from pET14b-HMG1 and and in with to the site of B was constructed by the sequence to domain B, from pT7-HMG1bB with NdeI and HindIII and in with to the site of were by DNA and of HMG1 boxes A and B were as described (19Bianchi M.E. Falciola L. Ferrari S. Lilley D.M.J. EMBO J. 1992; 11: 1055-1063Crossref PubMed Scopus (215) Google Scholar) that were using a in HMG1 box A at and box B at were and at His6-tagged HMG1 was in at for and as described for human TBP J. M. V. Egly J.-M. EMBO J. 1993; 12: PubMed Scopus Google Scholar). containing HMG1 were by using a in D. HMG1, which at was and at and of yeast and human TBP were as described J. P. F. Nucleic Acids Res. 1996; PubMed Scopus Google Scholar). TBP in were and on as described and on the of crude was used without human TFIIB was in and as described Reinberg D. Nature. 1991; PubMed Scopus Google Scholar). was from nuclear as described M. Roeder R.G. Cell. 1991; Full Text PDF PubMed Scopus Google Scholar). and box A and box B were and as suggested by the GST, box A, or box B were with in containing in was with the of were for 1 at with in a of of the with the proteins were by in were in to with specific and using was by the proteins and the TATA box for at J. P. F. Nucleic Acids Res. 1996; PubMed Scopus Google Scholar). of the an with the for the used were a and from P. was as described S. S. Nature. 1995; 376: PubMed Scopus Google Scholar). of the as for but were to and the was by were on and the from the by DNA was and in In were and as described J. M. V. Egly J.-M. EMBO J. 1993; 12: PubMed Scopus Google Scholar). The DNA was constructed by of a of containing a of the Gal4-binding site sequence and and to the by with of the previously described J. P. F. Nucleic Acids Res. 1996; PubMed Scopus Google Scholar). The involvement of HMG1 (and HMG2) in the transcription has long been a of and results have been reported. from II the of a pre-initiation complex This is by the recognition of the TATA box by TBP. and TFIIB the by several other factors the of basal factors II are to transcription G. T. Reinberg D. Genes Dev. 1996; PubMed Scopus Google Scholar). the of the role of HMG1 in II we have its involvement in several of the very of shown in 1 A, the interaction of HMG1 with human TBP was in an whereas not be using yeast TBP and that in the TBP interaction with the TATA box on its was very and be and and B 1 and as described S. Genes Dev. 1993; PubMed Scopus Google Scholar). The interaction of HMG1 with the complex to a clear complex 1 A, that HMG1 the binding of hTBP to the TATA this interaction also place with the complex to the complex the of HMG1 in the complex not result in a of electrophoretic mobility but of mobility between the and the with and HMG1 not significantly to DNA in the of TBP 1 A, and yeast a highly conserved C-terminal core with sequence whereas the domains not show any B shows that using human core TBP HMG1 interacts with and to a complex with electrophoretic mobility as shown The interaction of with HMG1 in this core TBP was also for interaction with HMG1 or in the of show that with TFIIB but not with HMG1, any by the The of increasing of HMG1 to with the of the complex 1 This in the of a complex containing and a very weak interaction that be observed with the full-length 1 A, of results that the core domain of hTBP the primary binding site for HMG1, in a not conserved in the yeast TBP. showed for a of the and at the and and and and and were was interaction with or but was a as the of HMG1 increased This at of have been reported to be more J. S. M. Roeder R.G. Mol. Cell. Biol. 1992; 12: PubMed Scopus Google Scholar), this a very weak interaction that to a defined as suggested The results were obtained the core of yeast and human were not the results suggest that HMG1 does not interact with and that binding on hTBP may be in The for the mobility of the complex may be that the of in the complex was from the and this the and were and with hTBP or TFIIB in are with the show the of hTBP in the complex and the of with that the of the complex with the was in the complex (and also in the with the complex and the used of hTBP C. S. Y. J. Egly J.-M. L. P. EMBO J. 1993; 12: PubMed Scopus Google Scholar), are to HMG1 in the and show that the complex be with the at a very of the the complex was not but at the the the complex the of HMG1 in the not be observed not HMG1 not These results suggest that TFIIB is the complex that the of the not the is sufficient to of the The three and and and were with as and are on a The of hTBP and TFIIB are on A The to and the sequence of the TATA box are on We obtained more on the of TFIIB in the by shows a clear hTBP the sequence in the three The from TFIIB and position be observed for the complex but was in the This that TFIIB is not to DNA in the of HMG1 and for the and the electrophoretic mobility of the complex shown In was for specific of HMG1 with DNA in any These results that the interaction of HMG1 with hTBP affects the interaction of TFIIB with We the hTBP in the interaction with HMG1 by the on the of hTBP that are not with DNA in the box of in all and mostly S. R. Genes Dev. 1994; PubMed Scopus Google provided by and showed on HMG1 interaction The in H2′ in to be and not be this a of provided by A. was S.K. Genes Dev. 1996; PubMed Scopus Google Scholar). We on H2′ and on the observed between human and yeast A using fusions to domains A and B of HMG1 was domain A, showed a clear interaction with wild hTBP domain B not show any for The interaction was not in any hTBP for the at position In this a was results have been observed in using full-length basal transcription in in vitro not of results that HMG1 interacts with human TBP by with its HMG box A to the H2′ of hTBP, as an TBP has been shown to in in the of several at one for polymerase; is TBP in the II TBP in the of a high molecular mass containing TBP and a of other shown in we have found that HMG box A can efficiently TFIID from crude nuclear as by the of hTBP and in the HMG box B not show any for any of TBP in the extracts. In similar we observed for interaction of HMG box A with the complex for an involvement of HMG1 mostly in II transcription not The of increasing of HMG1 to an in has already been shown to result in repression of both basal and activated transcription. However, to results of HMG1 or be H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google and 16Stelzer G. Goppelt A. Lottspeich F. Meisterernst M. Mol. Cell. Biol. 1994; 14: 4712-4721Crossref PubMed Scopus (55) Google and results not We Gal4-binding domain fusions to domains A and B of HMG1 to the of and the We used the proteins in transcription in vitro with a with binding or a with binding to a of box A and B in which was more on the box B in an repression activity the binding B, However, a was observed using the low was a activation was observed A, a was A, These suggest that on the domain B the PIC, may or transcription. the protein box A was more in transcription box B using the the and for box A and box B in of A, we can that box A is more box B in basal transcription. However, this practically the binding and on These results suggest a specific repression by domain A to the and in to domain B, the of box A showed any at any that boxes A and B, are not and that in II transcription in the of the HMG1 The involvement of HMG1 (and HMG2) in transcription has been for a long and results have been reported. on the and repression or activation of transcription has been vitro (11Ge H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google Scholar, S.A. Prendergast P. Wagner J.P. Nissen M. Reeves R. Pettijohn D.E. Edwards D.P. Mol. Cell. Biol. 1994; 14: 3376-3391Crossref PubMed Google Scholar, 16Stelzer G. Goppelt A. Lottspeich F. Meisterernst M. Mol. Cell. Biol. 1994; 14: 4712-4721Crossref PubMed Scopus (55) Google Scholar, 18Shykind B.M. Kim J. Sharp P.A. Genes Dev. 1995; 9: 1354-1365Crossref PubMed Scopus (130) Google Scholar). The conflicting results may be the of the of in vitro and or may from of HMG1 on the of genes. we have in the interaction of HMG1 with TBP in to on the of and Roeder (11Ge H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google Scholar) reported that HMG1 can interact with results were in with showed that this interaction is species-specific. The of the has been we that only box A of HMG1 interacts with This is to this domains A and B been shown to be for binding to and cisplatin-modified DNA D. Decoville M. Maurizot J.C. Bianchi M.E. Leng M. J. Mol. Biol. 1995; 246: 243-247Crossref PubMed Scopus (48) Google Scholar, M.E. Lilley D.M.J. DNA-Protein: Structural Interactions. Oxford University Press, Oxford1994: 177-200Google Scholar) and for with HOXD9 and Oct2 (9Zappavigna V. Falciola L. Citterich M.H. Mavilio F. Bianchi M.E. EMBO J. 1996; 15: 4981-4991Crossref PubMed Scopus (217) Google Scholar, 10Zwilling S. König H. Wirth T. EMBO J. 1995; 14: 1198-1208Crossref PubMed Scopus (218) Google Scholar). The of HMG box A in the interaction with hTBP is not molecular the of the L-shaped which has been shown to interact in the minor groove of DNA L. Lilley D.M.J. Bianchi M.E. Nucleic Acids Res. 1993; Scopus Google Scholar). HMG1 interacts with human TBP but not with yeast TBP, and the interaction takes place on the core domain. of the sequence a the TBP core domain was a to the In we H2′ of hTBP as the HMG1 primary binding a that from to the is conserved in yeast TBP TBP in we also not any interaction of HMG1 with TBP using not of affects the interaction with However, interaction can be that which are not conserved can in the binding of human is in yeast and in to also the interaction with HMG box A that in the to HMG1, shows only a very sequence (14Bianchi M.E. Lilley D.M.J. DNA-Protein: Structural Interactions. Oxford University Press, Oxford1994: 177-200Google Scholar). The is for the yeast of HMG1, proteins and which show a weak in the HMG box A domain J. R. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). both HMG1 and the core domain of TBP are conserved in and may interact in all The of hTBP to the interaction with HMG1, as suggested by the interaction of core TBP with full-length TBP and by the to of the of hTBP in the complex with the HMG1 can interact not only with TBP but also with TFIID. The is that the H2′ of TBP is interactions with be In any HMG box B does not interact TBP in the complex is not that any specific be to II HMG1 is from the transcription takes place L. F. S. G. R. Bianchi M.E. J. Biol. PubMed Scopus Google Scholar). In any the of interactions with other basal transcription factors of basal transcription factors and II are to the II Nature. 1996; PubMed Scopus Google Scholar, R. M. H. R. P. S. Reinberg D. Nature. 1996; PubMed Scopus Google Scholar, V. E.A. Cell. 1995; Full Text PDF PubMed Scopus Google Scholar). the has been reported to be efficiently repressed in vitro by the of Nature. 1996; PubMed Scopus Google Scholar). We found for the interaction of the II with HMG1, as the of or TFIIB was in with crude not The site of interaction of HMG1 on TBP very in to the TFIIB binding site on the C-terminal H. E.D. Roeder R.G. S.K. Nature. 1995; PubMed Scopus Google Scholar) It is also to the binding which has been mapped on the of TBP in the structure and on by S.K. Genes Dev. 1996; PubMed Scopus Google Scholar, H. X. Reinberg D. S. A. 1996; PubMed Scopus Google Scholar). The interaction is to of for the binding of human and yeast S. S. Science. 1996; PubMed Scopus Google Scholar, S. Y. Nature. 1996; PubMed Scopus Google Scholar). the known structures are with the effects we of HMG1 on TFIIB and binding to TBP HMG1 whereas HMG1 and TFIIB are not but TFIIB is with to the DNA and with to TBP more and TBP to specific We not the of TFIIB the to one of the or that have been to TFIIB Nature. 1994; PubMed Scopus Google Scholar) or an In any results suggest that in the TFIIB may be only on the hTBP C-terminal on the in In of this interaction of HMG box A or box B with TFIIB can be in not that of TFIIB binding to hTBP specific interaction of HMG1 with TFIIB but a HMG boxes in general and of HMG1 in are known to interact with DNA (5Bianchi M.E. Beltrame M. Paonessa G. Science. 1989; 243: 1056-1059Crossref PubMed Scopus (554) Google Scholar, 6Locker D. Decoville M. Maurizot J.C. Bianchi M.E. Leng M. J. Mol. Biol. 1995; 246: 243-247Crossref PubMed Scopus (48) Google Scholar, S. Harley V.R. Pontiggia A. Goodfellow P.N. Lovell-Badge R. Bianchi M.E. EMBO J. 1992; 11: 4497-4506Crossref PubMed Scopus (382) Google Scholar, 8Pöhler J.R.G. Norman D.G. Bramham J. Bianchi M.E. Lilley D.M.J. EMBO J. 1998; 17: 817-826Crossref PubMed Scopus (103) Google Scholar, M.E. Lilley D.M.J. DNA-Protein: Structural Interactions. Oxford University Press, Oxford1994: 177-200Google Scholar, L. Lilley D.M.J. Bianchi M.E. Nucleic Acids Res. 1993; Scopus Google Scholar). the electrophoretic mobility of the complex may a in the of the We that this is HMG1 an in the of DNA in the this result in a of not electrophoretic A in DNA is not to be from HMG1 in TBP interaction with the TATA which has not been In any the binding is of hTBP, and the on DNA, be a of this is to the of the DNA in the TFIIB is for II transcription and is also the for several G. T. Reinberg D. Genes Dev. 1996; PubMed Scopus Google L. Reinberg D. 1995; PubMed Scopus Google Scholar). The fact that HMG1 affects the interaction of TFIIB in the pre-initiation complex may its activity observed in vitro H. Roeder R.G. J. Biol. Chem. 1994; 269: 17136-17140Abstract Full Text PDF PubMed Google and 16Stelzer G. Goppelt A. Lottspeich F. Meisterernst M. Mol. Cell. Biol. 1994; 14: 4712-4721Crossref PubMed Scopus (55) Google this On the other the of the interaction by the of HMG1 on and II transcription. We have the of the HMG boxes of HMG1 on transcription from a in in this highly the results observed are HMG box B has a in solution at high and has or effects is recruited to the by to a DNA binding domain. A, on the shows only effects in both the interaction does not a as a of as is HMG1 interactions be for the of HMG1 may the with which interacts and proteins, nuclear hormone and (9Zappavigna V. Falciola L. Citterich M.H. Mavilio F. Bianchi M.E. EMBO J. 1996; 15: 4981-4991Crossref PubMed Scopus (217) Google Scholar, 10Zwilling S. König H. Wirth T. EMBO J. 1995; 14: 1198-1208Crossref PubMed Scopus (218) Google Scholar, L. Moorthy N.C. Murthy K.G.K. Manley J.L. Bustin M. Prives C. Genes Dev. 1998; 12: 462-472Crossref PubMed Scopus (284) Google Scholar, V. Melvin V. Prendergast P. Altmann M. Ronfani L. Bianchi M.E. Taraseviciene L. Nordeen S.K. Allegretto E.A. Edwards D.P. Mol. Cell. Biol. 1998; 18: 4471-4487Crossref PubMed Scopus (306) Google Scholar) to TFIID TFIIB and be by for In the of interactions the is complex that HMG1 have effects on the transcription of not as already shown B.M. Kim J. Sharp P.A. Genes Dev. 1995; 9: 1354-1365Crossref PubMed Scopus (130) Google Scholar), but in vivo as We R. G. P. J.-M. D. and A. J. for the of expression and specific We are very to F. J. and all members of and to A. B. J. and R. for and We also R. and the for and for and X. for