Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1996 Feb;16(2):503–512. doi: 10.1128/mcb.16.2.503

The major histocompatibility complex class II Ea promoter requires TFIID binding to an initiator sequence.

M Bellorini 1, J C Dantonel 1, J B Yoon 1, R G Roeder 1, L Tora 1, R Mantovani 1
PMCID: PMC231028  PMID: 8552077

Abstract

The major histocompatibility complex (MHC) class II Ea promoter is dependent on the presence of conserved upstream X and Y boxes and of initiator (Inr) sequences. In vitro transcription analysis of the Inr region with linker-scanning mutants pinpoints a functionally essential element that shows homology to the terminal deoxynucleotidyltransferase (TdT) Inr; contrary to the TdT Inr and other Inrs identified so far, the key sequence, between positions +5 and +12, is located within a transcribed area. Swapping the TdT sequence into the corresponding Ea position leads to a fivefold increase in transcription rate, without altering start site selection. Inr-binding proteins LBP-1/CP2 and TIP--a TdT Inr-binding protein unrelated to YY1--recognize the Ea Inr; they interact with overlapping yet distinct sequences around the Cap site, but their binding does not coincide with Ea Inr activity. A good correlation is, rather, found with binding of immunopurified holo-TFIID to this element. TFIID interacts both with Ea TATA-like and Inr sequences, but only the latter is functionally relevant. Unlike TBP, TFIID binds in the absence of TFIIA, indicating a stabilizing role for TBP-associated factors in Ea promoter recognition. Sequence comparison with other mouse and human MHC class II promoters suggests a common mechanism of start site(s) selection for the MHC class II gene family.

Full Text

The Full Text of this article is available as a PDF (536.8 KB).

Selected References

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

  1. Andersson G., Peterlin B. M. NF-X2 that binds to the DRA X2-box is activator protein 1. Expression cloning of c-Jun. J Immunol. 1990 Nov 15;145(10):3456–3462. [PubMed] [Google Scholar]
  2. Barton M. C., Madani N., Emerson B. M. The erythroid protein cGATA-1 functions with a stage-specific factor to activate transcription of chromatin-assembled beta-globin genes. Genes Dev. 1993 Sep;7(9):1796–1809. doi: 10.1101/gad.7.9.1796. [DOI] [PubMed] [Google Scholar]
  3. Benoist C., Mathis D. Regulation of major histocompatibility complex class-II genes: X, Y and other letters of the alphabet. Annu Rev Immunol. 1990;8:681–715. doi: 10.1146/annurev.iy.08.040190.003341. [DOI] [PubMed] [Google Scholar]
  4. Bray S. J., Burke B., Brown N. H., Hirsh J. Embryonic expression pattern of a family of Drosophila proteins that interact with a central nervous system regulatory element. Genes Dev. 1989 Aug;3(8):1130–1145. doi: 10.1101/gad.3.8.1130. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Brou C., Chaudhary S., Davidson I., Lutz Y., Wu J., Egly J. M., Tora L., Chambon P. Distinct TFIID complexes mediate the effect of different transcriptional activators. EMBO J. 1993 Feb;12(2):489–499. doi: 10.1002/j.1460-2075.1993.tb05681.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bucher P. Weight matrix descriptions of four eukaryotic RNA polymerase II promoter elements derived from 502 unrelated promoter sequences. J Mol Biol. 1990 Apr 20;212(4):563–578. doi: 10.1016/0022-2836(90)90223-9. [DOI] [PubMed] [Google Scholar]
  8. Cosgrove D., Gray D., Dierich A., Kaufman J., Lemeur M., Benoist C., Mathis D. Mice lacking MHC class II molecules. Cell. 1991 Sep 6;66(5):1051–1066. doi: 10.1016/0092-8674(91)90448-8. [DOI] [PubMed] [Google Scholar]
  9. Coustry F., Maity S. N., de Crombrugghe B. Studies on transcription activation by the multimeric CCAAT-binding factor CBF. J Biol Chem. 1995 Jan 6;270(1):468–475. doi: 10.1074/jbc.270.1.468. [DOI] [PubMed] [Google Scholar]
  10. DeJong J., Roeder R. G. A single cDNA, hTFIIA/alpha, encodes both the p35 and p19 subunits of human TFIIA. Genes Dev. 1993 Nov;7(11):2220–2234. doi: 10.1101/gad.7.11.2220. [DOI] [PubMed] [Google Scholar]
  11. Dedrick R. L., Jones P. P. Sequence elements required for activity of a murine major histocompatibility complex class II promoter bind common and cell-type-specific nuclear factors. Mol Cell Biol. 1990 Feb;10(2):593–604. doi: 10.1128/mcb.10.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dorn A., Bollekens J., Staub A., Benoist C., Mathis D. A multiplicity of CCAAT box-binding proteins. Cell. 1987 Sep 11;50(6):863–872. doi: 10.1016/0092-8674(87)90513-7. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Dynlacht B. D., Attardi L. D., Admon A., Freeman M., Tjian R. Functional analysis of NTF-1, a developmentally regulated Drosophila transcription factor that binds neuronal cis elements. Genes Dev. 1989 Nov;3(11):1677–1688. doi: 10.1101/gad.3.11.1677. [DOI] [PubMed] [Google Scholar]
  15. Emanuel P. A., Gilmour D. S. Transcription factor TFIID recognizes DNA sequences downstream of the TATA element in the Hsp70 heat shock gene. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8449–8453. doi: 10.1073/pnas.90.18.8449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gilfillan S., Dierich A., Lemeur M., Benoist C., Mathis D. Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science. 1993 Aug 27;261(5125):1175–1178. doi: 10.1126/science.8356452. [DOI] [PubMed] [Google Scholar]
  17. Glimcher L. H., Kara C. J. Sequences and factors: a guide to MHC class-II transcription. Annu Rev Immunol. 1992;10:13–49. doi: 10.1146/annurev.iy.10.040192.000305. [DOI] [PubMed] [Google Scholar]
  18. Grosveld F., Antoniou M., Berry M., de Boer E., Dillon N., Ellis J., Fraser P., Hurst J., Imam A., Meijer D. Regulation of human globin gene switching. Cold Spring Harb Symp Quant Biol. 1993;58:7–13. doi: 10.1101/sqb.1993.058.01.004. [DOI] [PubMed] [Google Scholar]
  19. Hahn S., Buratowski S., Sharp P. A., Guarente L. Yeast TATA-binding protein TFIID binds to TATA elements with both consensus and nonconsensus DNA sequences. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5718–5722. doi: 10.1073/pnas.86.15.5718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hai T. W., Horikoshi M., Roeder R. G., Green M. R. Analysis of the role of the transcription factor ATF in the assembly of a functional preinitiation complex. Cell. 1988 Sep 23;54(7):1043–1051. doi: 10.1016/0092-8674(88)90119-5. [DOI] [PubMed] [Google Scholar]
  21. Horikoshi M., Hai T., Lin Y. S., Green M. R., Roeder R. G. Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex. Cell. 1988 Sep 23;54(7):1033–1042. doi: 10.1016/0092-8674(88)90118-3. [DOI] [PubMed] [Google Scholar]
  22. Hsiao K. M., McMahon S. L., Farnham P. J. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994 Jul 1;8(13):1526–1537. doi: 10.1101/gad.8.13.1526. [DOI] [PubMed] [Google Scholar]
  23. Ivashkiv L. B., Liou H. C., Kara C. J., Lamph W. W., Verma I. M., Glimcher L. H. mXBP/CRE-BP2 and c-Jun form a complex which binds to the cyclic AMP, but not to the 12-O-tetradecanoylphorbol-13-acetate, response element. Mol Cell Biol. 1990 Apr;10(4):1609–1621. doi: 10.1128/mcb.10.4.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Jacq X., Brou C., Lutz Y., Davidson I., Chambon P., Tora L. Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell. 1994 Oct 7;79(1):107–117. doi: 10.1016/0092-8674(94)90404-9. [DOI] [PubMed] [Google Scholar]
  25. Jane S. M., Nienhuis A. W., Cunningham J. M. Hemoglobin switching in man and chicken is mediated by a heteromeric complex between the ubiquitous transcription factor CP2 and a developmentally specific protein. EMBO J. 1995 Jan 3;14(1):97–105. doi: 10.1002/j.1460-2075.1995.tb06979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Kato H., Horikoshi M., Roeder R. G. Repression of HIV-1 transcription by a cellular protein. Science. 1991 Mar 22;251(5000):1476–1479. doi: 10.1126/science.2006421. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Kim J. L., Nikolov D. B., Burley S. K. Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature. 1993 Oct 7;365(6446):520–527. doi: 10.1038/365520a0. [DOI] [PubMed] [Google Scholar]
  30. Kouskoff V., Mantovani R. M., Candéias S. M., Dorn A., Staub A., Lisowska-Grospierre B., Griscelli C., Benoist C. O., Mathis D. J. NF-X, a transcription factor implicated in MHC class II gene regulation. J Immunol. 1991 May 1;146(9):3197–3204. [PubMed] [Google Scholar]
  31. Lieberman P. M., Berk A. J. A mechanism for TAFs in transcriptional activation: activation domain enhancement of TFIID-TFIIA--promoter DNA complex formation. Genes Dev. 1994 May 1;8(9):995–1006. doi: 10.1101/gad.8.9.995. [DOI] [PubMed] [Google Scholar]
  32. Lim L. C., Swendeman S. L., Sheffery M. Molecular cloning of the alpha-globin transcription factor CP2. Mol Cell Biol. 1992 Feb;12(2):828–835. doi: 10.1128/mcb.12.2.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mai S., Mårtensson I. L. The c-myc protein represses the lambda 5 and TdT initiators. Nucleic Acids Res. 1995 Jan 11;23(1):1–9. doi: 10.1093/nar/23.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mantovani R., Pessara U., Tronche F., Li X. Y., Knapp A. M., Pasquali J. L., Benoist C., Mathis D. Monoclonal antibodies to NF-Y define its function in MHC class II and albumin gene transcription. EMBO J. 1992 Sep;11(9):3315–3322. doi: 10.1002/j.1460-2075.1992.tb05410.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mantovani R., Tora L., Moncollin V., Egly J. M., Benoist C., Mathis D. The major histocompatibility complex (MHC) Ea promoter: sequences and factors at the initiation site. Nucleic Acids Res. 1993 Oct 25;21(21):4873–4878. doi: 10.1093/nar/21.21.4873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Matsushima G. K., Itoh-Lindstrom Y., Ting J. P. Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. Mol Cell Biol. 1992 Dec;12(12):5610–5619. doi: 10.1128/mcb.12.12.5610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Means A. L., Farnham P. J. Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site. Mol Cell Biol. 1990 Feb;10(2):653–661. doi: 10.1128/mcb.10.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mengus G., May M., Jacq X., Staub A., Tora L., Chambon P., Davidson I. Cloning and characterization of hTAFII18, hTAFII20 and hTAFII28: three subunits of the human transcription factor TFIID. EMBO J. 1995 Apr 3;14(7):1520–1531. doi: 10.1002/j.1460-2075.1995.tb07138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Milos P. M., Zaret K. S. A ubiquitous factor is required for C/EBP-related proteins to form stable transcription complexes on an albumin promoter segment in vitro. Genes Dev. 1992 Jun;6(6):991–1004. doi: 10.1101/gad.6.6.991. [DOI] [PubMed] [Google Scholar]
  41. O'Shea-Greenfield A., Smale S. T. Roles of TATA and initiator elements in determining the start site location and direction of RNA polymerase II transcription. J Biol Chem. 1992 Jan 15;267(2):1391–1402. [PubMed] [Google Scholar]
  42. Ozer J., Moore P. A., Bolden A. H., Lee A., Rosen C. A., Lieberman P. M. Molecular cloning of the small (gamma) subunit of human TFIIA reveals functions critical for activated transcription. Genes Dev. 1994 Oct 1;8(19):2324–2335. doi: 10.1101/gad.8.19.2324. [DOI] [PubMed] [Google Scholar]
  43. Parada C. A., Yoon J. B., Roeder R. G. A novel LBP-1-mediated restriction of HIV-1 transcription at the level of elongation in vitro. J Biol Chem. 1995 Feb 3;270(5):2274–2283. doi: 10.1074/jbc.270.5.2274. [DOI] [PubMed] [Google Scholar]
  44. Pugh B. F., Tjian R. Transcription from a TATA-less promoter requires a multisubunit TFIID complex. Genes Dev. 1991 Nov;5(11):1935–1945. doi: 10.1101/gad.5.11.1935. [DOI] [PubMed] [Google Scholar]
  45. Purnell B. A., Emanuel P. A., Gilmour D. S. TFIID sequence recognition of the initiator and sequences farther downstream in Drosophila class II genes. Genes Dev. 1994 Apr 1;8(7):830–842. doi: 10.1101/gad.8.7.830. [DOI] [PubMed] [Google Scholar]
  46. Reith W., Herrero-Sanchez C., Kobr M., Silacci P., Berte C., Barras E., Fey S., Mach B. MHC class II regulatory factor RFX has a novel DNA-binding domain and a functionally independent dimerization domain. Genes Dev. 1990 Sep;4(9):1528–1540. doi: 10.1101/gad.4.9.1528. [DOI] [PubMed] [Google Scholar]
  47. Reith W., Siegrist C. A., Durand B., Barras E., Mach B. Function of major histocompatibility complex class II promoters requires cooperative binding between factors RFX and NF-Y. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):554–558. doi: 10.1073/pnas.91.2.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. 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]
  51. Smale S. T., Schmidt M. C., Berk A. J., Baltimore D. Transcriptional activation by Sp1 as directed through TATA or initiator: specific requirement for mammalian transcription factor IID. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4509–4513. doi: 10.1073/pnas.87.12.4509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sypes M. A., Gilmour D. S. Protein/DNA crosslinking of a TFIID complex reveals novel interactions downstream of the transcription start. Nucleic Acids Res. 1994 Mar 11;22(5):807–814. doi: 10.1093/nar/22.5.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Tjian R., Maniatis T. Transcriptional activation: a complex puzzle with few easy pieces. Cell. 1994 Apr 8;77(1):5–8. doi: 10.1016/0092-8674(94)90227-5. [DOI] [PubMed] [Google Scholar]
  54. 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]
  55. Verrijzer C. P., Yokomori K., Chen J. L., Tjian R. Drosophila TAFII150: similarity to yeast gene TSM-1 and specific binding to core promoter DNA. Science. 1994 May 13;264(5161):933–941. doi: 10.1126/science.8178153. [DOI] [PubMed] [Google Scholar]
  56. Viville S., Jongeneel V., Koch W., Mantovani R., Benoist C., Mathis D. The E alpha promoter: a linker-scanning analysis. J Immunol. 1991 May 1;146(9):3211–3217. [PubMed] [Google Scholar]
  57. Viville S., Mantovani R. S1 mapping using single-stranded DNA probes. Methods Mol Biol. 1994;31:299–305. doi: 10.1385/0-89603-258-2:299. [DOI] [PubMed] [Google Scholar]
  58. Weis L., Reinberg D. Transcription by RNA polymerase II: initiator-directed formation of transcription-competent complexes. FASEB J. 1992 Nov;6(14):3300–3309. doi: 10.1096/fasebj.6.14.1426767. [DOI] [PubMed] [Google Scholar]
  59. 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]
  60. Wobbe C. R., Struhl K. Yeast and human TATA-binding proteins have nearly identical DNA sequence requirements for transcription in vitro. Mol Cell Biol. 1990 Aug;10(8):3859–3867. doi: 10.1128/mcb.10.8.3859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Wong J. M., Bateman E. TBP-DNA interactions in the minor groove discriminate between A:T and T:A base pairs. Nucleic Acids Res. 1994 May 25;22(10):1890–1896. doi: 10.1093/nar/22.10.1890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Yoon J. B., Li G., Roeder R. G. Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro. Mol Cell Biol. 1994 Mar;14(3):1776–1785. doi: 10.1128/mcb.14.3.1776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Zawel L., Reinberg D. Initiation of transcription by RNA polymerase II: a multi-step process. Prog Nucleic Acid Res Mol Biol. 1993;44:67–108. doi: 10.1016/s0079-6603(08)60217-2. [DOI] [PubMed] [Google Scholar]
  64. Zenzie-Gregory B., Khachi A., Garraway I. P., Smale S. T. Mechanism of initiator-mediated transcription: evidence for a functional interaction between the TATA-binding protein and DNA in the absence of a specific recognition sequence. Mol Cell Biol. 1993 Jul;13(7):3841–3849. doi: 10.1128/mcb.13.7.3841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Zenzie-Gregory B., Sheridan P., Jones K. A., Smale S. T. HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site. J Biol Chem. 1993 Jul 25;268(21):15823–15832. [PubMed] [Google Scholar]
  66. Zhou Q., Lieberman P. M., Boyer T. G., Berk A. J. Holo-TFIID supports transcriptional stimulation by diverse activators and from a TATA-less promoter. Genes Dev. 1992 Oct;6(10):1964–1974. doi: 10.1101/gad.6.10.1964. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES