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Proc Natl Acad Sci U S A. Jun 1987; 84(12): 4254–4258.
PMCID: PMC305063

Upstream DNA sequences required for tissue-specific expression of the HLA-DR alpha gene.


We have used in vitro deletion mutagenesis in combination with DNA transfection to search for cis-acting regulatory elements involved in the tissue-specific expression of a human class II major histocompatibility complex gene. A 140-base-pair 5' flanking fragment that contains the class II box consensus sequences and an octamer sequence (ATTTGCAT) confers tissue specificity on the promoter of the HLA-DR alpha gene. Recombinant DNA plasmids containing this DR alpha gene segment fused to the coding sequence of the bacterial chloramphenicol acetyltransferase gene are expressed at higher levels in human B-cell lines than in human T-cell lines. We have demonstrated that the most 5' of the class II boxes is essential for tissue-specific DR alpha promoter function. In addition, using an electrophoretic mobility shift assay to identify DNA binding proteins, we have detected binding of nuclear proteins to DNA probes containing the class II boxes and the octamer sequence. A protein that binds to the octamer is present at higher levels in nuclear extracts of B-cell lines than in other cell lines examined. This protein may be important for the tissue-specific expression of the HLA-DR alpha gene.

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  • Rosenthal AS, Shevach EM. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. [PMC free article] [PubMed]
  • Houghton AN, Thomson TM, Gross D, Oettgen HF, Old LJ. Surface antigens of melanoma and melanocytes. Specificity of induction of Ia antigens by human gamma-interferon. J Exp Med. 1984 Jul 1;160(1):255–269. [PMC free article] [PubMed]
  • Kaufman JF, Auffray C, Korman AJ, Shackelford DA, Strominger J. The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1–13. [PubMed]
  • Unanue ER, Beller DI, Lu CY, Allen PM. Antigen presentation: comments on its regulation and mechanism. J Immunol. 1984 Jan;132(1):1–5. [PubMed]
  • Roehm NW, Leibson HJ, Zlotnik A, Kappler J, Marrack P, Cambier JC. Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med. 1984 Sep 1;160(3):679–694. [PMC free article] [PubMed]
  • Gillies SD, Folsom V, Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. [PubMed]
  • Basta PV, Sherman PA, Ting JP. Identification of an interferon-gamma response region 5' of the human histocompatibility leukocyte antigen DR alpha chain gene which is active in human glioblastoma multiforme lines. J Immunol. 1987 Feb 15;138(4):1275–1280. [PubMed]
  • Boss JM, Strominger JL. Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9139–9143. [PMC free article] [PubMed]
  • Friedman RL, Stark GR. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature. 1985 Apr 18;314(6012):637–639. [PubMed]
  • Saito H, Maki RA, Clayton LK, Tonegawa S. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520–5524. [PMC free article] [PubMed]
  • Parslow TG, Blair DL, Murphy WJ, Granner DK. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci U S A. 1984 May;81(9):2650–2654. [PMC free article] [PubMed]
  • Bergman Y, Rice D, Grosschedl R, Baltimore D. Two regulatory elements for immunoglobulin kappa light chain gene expression. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7041–7045. [PMC free article] [PubMed]
  • Falkner FG, Zachau HG. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. [PubMed]
  • Queen C, Stafford J. Fine mapping of an immunoglobulin gene activator. Mol Cell Biol. 1984 Jun;4(6):1042–1049. [PMC free article] [PubMed]
  • Gorman CM, Moffat LF, Howard BH. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. [PMC free article] [PubMed]
  • Walker MD, Edlund T, Boulet AM, Rutter WJ. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. [PubMed]
  • Sompayrac LM, Danna KJ. Efficient infection of monkey cells with DNA of simian virus 40. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7575–7578. [PMC free article] [PubMed]
  • Fried M, Crothers DM. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. [PMC free article] [PubMed]
  • Garner MM, Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. [PMC free article] [PubMed]
  • Strauss F, Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. [PubMed]
  • Singh H, Sen R, Baltimore D, Sharp PA. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes. Nature. 1986 Jan 9;319(6049):154–158. [PubMed]
  • Dignam JD, Lebovitz RM, Roeder RG. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. [PMC free article] [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Staudt LM, Singh H, Sen R, Wirth T, Sharp PA, Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. [PubMed]
  • Breathnach R, Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. [PubMed]
  • Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. [PubMed]
  • Landolfi NF, Capra JD, Tucker PW. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature. 1986 Oct 9;323(6088):548–551. [PubMed]
  • Gladstone P, Pious D. Identification of a trans-acting function regulation HLA-DR expression in a DR-negative B cell variant. Somatic Cell Genet. 1980 Mar;6(2):285–298. [PubMed]
  • Accolla RS, Carra G, Guardiola J. Reactivation by a trans-acting factor of human major histocompatibility complex Ia gene expression in interspecies hybrids between an Ia-negative human B-cell variant and an Ia-positive mouse B-cell lymphoma. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5145–5149. [PMC free article] [PubMed]
  • Larhammar D, Servenius B, Rask L, Peterson PA. Characterization of an HLA DR beta pseudogene. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1475–1479. [PMC free article] [PubMed]
  • Boss JM, Strominger JL. Cloning and sequence analysis of the human major histocompatibility complex gene DC-3 beta. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5199–5203. [PMC free article] [PubMed]
  • Larhammar D, Hammerling U, Denaro M, Lund T, Flavell RA, Rask L, Peterson PA. Structure of the murine immune response I-A beta locus: sequence of the I-A beta gene and an adjacent beta-chain second domain exon. Cell. 1983 Aug;34(1):179–188. [PubMed]
  • O'Sullivan DM, Larhammar D, Wilson MC, Peterson PA, Quaranta V. Structure of the human Ia-associated invariant (gamma)-chain gene: identification of 5' sequences shared with major histocompatibility complex class II genes. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4484–4488. [PMC free article] [PubMed]
  • Sive HL, Roeder RG. Interaction of a common factor with conserved promoter and enhancer sequences in histone H2B, immunoglobulin, and U2 small nuclear RNA (snRNA) genes. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6382–6386. [PMC free article] [PubMed]
  • Ares M, Jr, Mangin M, Weiner AM. Orientation-dependent transcriptional activator upstream of a human U2 snRNA gene. Mol Cell Biol. 1985 Jul;5(7):1560–1570. [PMC free article] [PubMed]
  • Mattaj IW, Lienhard S, Jiricny J, De Robertis EM. An enhancer-like sequence within the Xenopus U2 gene promoter facilitates the formation of stable transcription complexes. Nature. 1985 Jul 11;316(6024):163–167. [PubMed]
  • Krol A, Lund E, Dahlberg JE. The two embryonic U1 RNA genes of Xenopus laevis have both common and gene-specific transcription signals. EMBO J. 1985 Jun;4(6):1529–1535. [PMC free article] [PubMed]
  • Ciliberto G, Buckland R, Cortese R, Philipson L. Transcription signals in embryonic Xenopus laevis U1 RNA genes. EMBO J. 1985 Jun;4(6):1537–1543. [PMC free article] [PubMed]

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