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. 1997 Dec 1;16(23):7091–7104. doi: 10.1093/emboj/16.23.7091

Cloning of an inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF1.

A L Roy 1, H Du 1, P D Gregor 1, C D Novina 1, E Martinez 1, R G Roeder 1
PMCID: PMC1170311  PMID: 9384587

Abstract

The transcription factor TFII-I has been shown to bind independently to two distinct promoter elements, a pyrimidine-rich initiator (Inr) and a recognition site (E-box) for upstream stimulatory factor 1 (USF1), and to stimulate USF1 binding to both of these sites. Here we describe the isolation of a cDNA encoding TFII-I and demonstrate that the corresponding 120 kDa polypeptide, when expressed ectopically, is capable of binding to both Inr and E-box elements. The primary structure of TFII-I reveals novel features that include six directly repeated 90 residue motifs that each possess a potential helix-loop/span-helix homology. These unique structural features suggest that TFII-I may have the capacity for multiple protein-protein and, potentially, multiple protein-DNA interactions. Consistent with this hypothesis and with previous in vitro studies, we further demonstrate that ectopic TFII-I and USF1 can act synergistically, and in some cases independently, to activate transcription in vivo through both Inr and the E-box elements of the adenovirus major late promoter. We also describe domains of USF1 that are necessary for its independent and synergistic activation functions.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  2. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiang C. M., Roeder R. G. Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science. 1995 Jan 27;267(5197):531–536. doi: 10.1126/science.7824954. [DOI] [PubMed] [Google Scholar]
  4. Conaway R. C., Conaway J. W. General initiation factors for RNA polymerase II. Annu Rev Biochem. 1993;62:161–190. doi: 10.1146/annurev.bi.62.070193.001113. [DOI] [PubMed] [Google Scholar]
  5. Dignam J. D., Martin P. L., Shastry B. S., Roeder R. G. Eukaryotic gene transcription with purified components. Methods Enzymol. 1983;101:582–598. doi: 10.1016/0076-6879(83)01039-3. [DOI] [PubMed] [Google Scholar]
  6. Du H., Roy A. L., Roeder R. G. Human transcription factor USF stimulates transcription through the initiator elements of the HIV-1 and the Ad-ML promoters. EMBO J. 1993 Feb;12(2):501–511. doi: 10.1002/j.1460-2075.1993.tb05682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferré-D'Amaré A. R., Pognonec P., Roeder R. G., Burley S. K. Structure and function of the b/HLH/Z domain of USF. EMBO J. 1994 Jan 1;13(1):180–189. doi: 10.1002/j.1460-2075.1994.tb06247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferré-D'Amaré A. R., Prendergast G. C., Ziff E. B., Burley S. K. Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain. Nature. 1993 May 6;363(6424):38–45. doi: 10.1038/363038a0. [DOI] [PubMed] [Google Scholar]
  9. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  10. Grueneberg D. A., Henry R. W., Brauer A., Novina C. D., Cheriyath V., Roy A. L., Gilman M. A multifunctional DNA-binding protein that promotes the formation of serum response factor/homeodomain complexes: identity to TFII-I. Genes Dev. 1997 Oct 1;11(19):2482–2493. doi: 10.1101/gad.11.19.2482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hu Y. F., Lüscher B., Admon A., Mermod N., Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990 Oct;4(10):1741–1752. doi: 10.1101/gad.4.10.1741. [DOI] [PubMed] [Google Scholar]
  12. Javahery R., Khachi A., Lo K., Zenzie-Gregory B., Smale S. T. DNA sequence requirements for transcriptional initiator activity in mammalian cells. Mol Cell Biol. 1994 Jan;14(1):116–127. doi: 10.1128/mcb.14.1.116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaufmann J., Smale S. T. Direct recognition of initiator elements by a component of the transcription factor IID complex. Genes Dev. 1994 Apr 1;8(7):821–829. doi: 10.1101/gad.8.7.821. [DOI] [PubMed] [Google Scholar]
  14. Kaufmann J., Verrijzer C. P., Shao J., Smale S. T. CIF, an essential cofactor for TFIID-dependent initiator function. Genes Dev. 1996 Apr 1;10(7):873–886. doi: 10.1101/gad.10.7.873. [DOI] [PubMed] [Google Scholar]
  15. Kirschbaum B. J., Pognonec P., Roeder R. G. Definition of the transcriptional activation domain of recombinant 43-kilodalton USF. Mol Cell Biol. 1992 Nov;12(11):5094–5101. doi: 10.1128/mcb.12.11.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lathe R. Synthetic oligonucleotide probes deduced from amino acid sequence data. Theoretical and practical considerations. J Mol Biol. 1985 May 5;183(1):1–12. doi: 10.1016/0022-2836(85)90276-1. [DOI] [PubMed] [Google Scholar]
  17. Lu H., Reach M. D., Minaya E., Young C. S. The initiator element of the adenovirus major late promoter has an important role in transcription initiation in vivo. J Virol. 1997 Jan;71(1):102–109. doi: 10.1128/jvi.71.1.102-109.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Luo X., Sawadogo M. Functional domains of the transcription factor USF2: atypical nuclear localization signals and context-dependent transcriptional activation domains. Mol Cell Biol. 1996 Apr;16(4):1367–1375. doi: 10.1128/mcb.16.4.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Manzano-Winkler B., Novina C. D., Roy A. L. TFII is required for transcription of the naturally TATA-less but initiator-containing Vbeta promoter. J Biol Chem. 1996 May 17;271(20):12076–12081. doi: 10.1074/jbc.271.20.12076. [DOI] [PubMed] [Google Scholar]
  20. Martinez E., Chiang C. M., Ge H., Roeder R. G. TATA-binding protein-associated factor(s) in TFIID function through the initiator to direct basal transcription from a TATA-less class II promoter. EMBO J. 1994 Jul 1;13(13):3115–3126. doi: 10.1002/j.1460-2075.1994.tb06610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Martinez E., Zhou Q., L'Etoile N. D., Oelgeschläger T., Berk A. J., Roeder R. G. Core promoter-specific function of a mutant transcription factor TFIID defective in TATA-box binding. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11864–11868. doi: 10.1073/pnas.92.25.11864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Meisterernst M., Roeder R. G. Family of proteins that interact with TFIID and regulate promoter activity. Cell. 1991 Nov 1;67(3):557–567. doi: 10.1016/0092-8674(91)90530-c. [DOI] [PubMed] [Google Scholar]
  23. Molkentin J. D., Black B. L., Martin J. F., Olson E. N. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell. 1995 Dec 29;83(7):1125–1136. doi: 10.1016/0092-8674(95)90139-6. [DOI] [PubMed] [Google Scholar]
  24. Molkentin J. D., Olson E. N. Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9366–9373. doi: 10.1073/pnas.93.18.9366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Novina C. D., Roy A. L. Core promoters and transcriptional control. Trends Genet. 1996 Sep;12(9):351–355. [PubMed] [Google Scholar]
  26. Orphanides G., Lagrange T., Reinberg D. The general transcription factors of RNA polymerase II. Genes Dev. 1996 Nov 1;10(21):2657–2683. doi: 10.1101/gad.10.21.2657. [DOI] [PubMed] [Google Scholar]
  27. Outram S. V., Owen M. J. The helix-loop-helix containing transcription factor USF activates the promoter of the CD2 gene. J Biol Chem. 1994 Oct 21;269(42):26525–26530. [PubMed] [Google Scholar]
  28. Pognonec P., Roeder R. G. Recombinant 43-kDa USF binds to DNA and activates transcription in a manner indistinguishable from that of natural 43/44-kDa USF. Mol Cell Biol. 1991 Oct;11(10):5125–5136. doi: 10.1128/mcb.11.10.5125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ptashne M., Gann A. Transcriptional activation by recruitment. Nature. 1997 Apr 10;386(6625):569–577. doi: 10.1038/386569a0. [DOI] [PubMed] [Google Scholar]
  30. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  31. Roeder R. G. The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem Sci. 1996 Sep;21(9):327–335. [PubMed] [Google Scholar]
  32. Roy A. L., Carruthers C., Gutjahr T., Roeder R. G. Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature. 1993 Sep 23;365(6444):359–361. doi: 10.1038/365359a0. [DOI] [PubMed] [Google Scholar]
  33. Roy A. L., Malik S., Meisterernst M., Roeder R. G. An alternative pathway for transcription initiation involving TFII-I. Nature. 1993 Sep 23;365(6444):355–359. doi: 10.1038/365355a0. [DOI] [PubMed] [Google Scholar]
  34. Roy A. L., Meisterernst M., Pognonec P., Roeder R. G. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Nature. 1991 Nov 21;354(6350):245–248. doi: 10.1038/354245a0. [DOI] [PubMed] [Google Scholar]
  35. Roy A. L., Roeder R. G. Initiator element binding protein TFII-I: a tale of two sites. Indian J Biochem Biophys. 1994 Feb;31(1):14–19. [PubMed] [Google Scholar]
  36. Sawadogo M., Roeder R. G. Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell. 1985 Nov;43(1):165–175. doi: 10.1016/0092-8674(85)90021-2. [DOI] [PubMed] [Google Scholar]
  37. Sawadogo M., Van Dyke M. W., Gregor P. D., Roeder R. G. Multiple forms of the human gene-specific transcription factor USF. I. Complete purification and identification of USF from HeLa cell nuclei. J Biol Chem. 1988 Aug 25;263(24):11985–11993. [PubMed] [Google Scholar]
  38. Scheidereit C., Cromlish J. A., Gerster T., Kawakami K., Balmaceda C. G., Currie R. A., Roeder R. G. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature. 1988 Dec 8;336(6199):551–557. doi: 10.1038/336551a0. [DOI] [PubMed] [Google Scholar]
  39. Seto E., Shi Y., Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991 Nov 21;354(6350):241–245. doi: 10.1038/354241a0. [DOI] [PubMed] [Google Scholar]
  40. Shore P., Sharrocks A. D. The MADS-box family of transcription factors. Eur J Biochem. 1995 Apr 1;229(1):1–13. doi: 10.1111/j.1432-1033.1995.tb20430.x. [DOI] [PubMed] [Google Scholar]
  41. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  42. Smale S. T. Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes. Biochim Biophys Acta. 1997 Mar 20;1351(1-2):73–88. doi: 10.1016/s0167-4781(96)00206-0. [DOI] [PubMed] [Google Scholar]
  43. Triezenberg S. J. Structure and function of transcriptional activation domains. Curr Opin Genet Dev. 1995 Apr;5(2):190–196. doi: 10.1016/0959-437x(95)80007-7. [DOI] [PubMed] [Google Scholar]
  44. Usheva A., Shenk T. TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA. Cell. 1994 Mar 25;76(6):1115–1121. doi: 10.1016/0092-8674(94)90387-5. [DOI] [PubMed] [Google Scholar]
  45. Verrijzer C. P., Chen J. L., Yokomori K., Tjian R. Binding of TAFs to core elements directs promoter selectivity by RNA polymerase II. Cell. 1995 Jun 30;81(7):1115–1125. doi: 10.1016/s0092-8674(05)80016-9. [DOI] [PubMed] [Google Scholar]
  46. Verrijzer C. P., Tjian R. TAFs mediate transcriptional activation and promoter selectivity. Trends Biochem Sci. 1996 Sep;21(9):338–342. [PubMed] [Google Scholar]
  47. Weintraub H., Genetta T., Kadesch T. Tissue-specific gene activation by MyoD: determination of specificity by cis-acting repression elements. Genes Dev. 1994 Sep 15;8(18):2203–2211. doi: 10.1101/gad.8.18.2203. [DOI] [PubMed] [Google Scholar]
  48. Wiley S. R., Kraus R. J., Mertz J. E. Functional binding of the "TATA" box binding component of transcription factor TFIID to the -30 region of TATA-less promoters. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5814–5818. doi: 10.1073/pnas.89.13.5814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yang W., Desiderio S. BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):604–609. doi: 10.1073/pnas.94.2.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zawel L., Reinberg D. Common themes in assembly and function of eukaryotic transcription complexes. Annu Rev Biochem. 1995;64:533–561. doi: 10.1146/annurev.bi.64.070195.002533. [DOI] [PubMed] [Google Scholar]

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