Restriction of interferon gamma responsiveness and basal expression of the myeloid human Fc gamma R1b gene is mediated by a functional PU.1 site and a transcription initiator consensus (original) (raw)
- Journal List
- J Exp Med
- v.179(6); 1994 Jun 1
- PMC2191524
J Exp Med. 1994 Jun 1; 179(6): 1985–1996.
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Abstract
The restricted expression of the human Fc gamma R1b gene to myeloid cells is likely to be regulated by a combination of transcription factors that may not be solely expressed in myeloid cells, but act together to restrict the expression of the gene to myeloid cells. Low basal expression of the human Fc gamma R1b gene is specifically upregulated by interferon gamma (IFN-gamma). A 181-bp region of 5' flanking sequence contains several key regulatory motifs that include the extended gamma response region (XGRR) and the PIE region. The XGRR contains the 39-bp gamma response region originally defined in the highly homologous Fc gamma R1a gene. The XGRR is in close proximity to the 21-bp PIE motif that is conserved in the promoters of some other myeloid genes. The PIE motif contains a consensus site for the macrophage and B cell transcription factor, PU.1, and is adjacent to the cluster of transcription start sites. An active transcription initiator, Inr, consensus spans the start sites and appears to direct transcription initiation of this TATA-less gene. In this study, we demonstrate that the PIE region contains a functional PU.1 site that binds a human PU.1-like protein and that associated factors present in myeloid extracts also bind in this PIE region. Mutational analysis reveals an absolute requirement for an intact PU.1 box for both basal and IFN-gamma inducible expression of this gene. In addition, mutations in the Inr greatly reduce basal and inducible transcription. Insertion of a strong TATA box downstream from the Inr or at -30 bp from the transcription start sites restores basal and inducible activity in the presence of a mutated PU.1 site. We also demonstrate that indeed, when the XGRR is positioned in the context of a heterologous TATA containing promoter, it is able to respond equivalently to either IFN-alpha or IFN- gamma. However, IFN-alpha responsiveness does not occur in the context of the physiological Fc gamma R1b TATA-less basal promoter. Our results suggest that a human PU.1-like factor acts as a "bridging factor" between the upstream IFN-gamma enhancer and the Inr dependent preinitiation complex. These findings indicate that the structure of the basal promoter in combination with restricted activators like PU.1 are important in regulating the expression of this gene.
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Selected References
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- Pearse RN, Feinman R, Ravetch JV. Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: transcriptional induction by gamma-interferon is mediated through common DNA response elements. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11305–11309. [PMC free article] [PubMed] [Google Scholar]
- Benech PD, Sastry K, Iyer RR, Eichbaum QG, Raveh DP, Ezekowitz RA. Definition of interferon gamma-response elements in a novel human Fc gamma receptor gene (Fc gamma RIb) and characterization of the gene structure. J Exp Med. 1992 Oct 1;176(4):1115–1123. [PMC free article] [PubMed] [Google Scholar]
- Wilson KC, Finbloom DS. Interferon gamma rapidly induces in human monocytes a DNA-binding factor that recognizes the gamma response region within the promoter of the gene for the high-affinity Fc gamma receptor. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11964–11968. [PMC free article] [PubMed] [Google Scholar]
- Schindler C, Shuai K, Prezioso VR, Darnell JE., Jr Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992 Aug 7;257(5071):809–813. [PubMed] [Google Scholar]
- Shuai K, Schindler C, Prezioso VR, Darnell JE., Jr Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992 Dec 11;258(5089):1808–1812. [PubMed] [Google Scholar]
- Shuai K, Stark GR, Kerr IM, Darnell JE., Jr A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993 Sep 24;261(5129):1744–1746. [PubMed] [Google Scholar]
- Fu XY, Schindler C, Improta T, Aebersold R, Darnell JE., Jr The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7840–7843. [PMC free article] [PubMed] [Google Scholar]
- Kessler DS, Veals SA, Fu XY, Levy DE. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev. 1990 Oct;4(10):1753–1765. [PubMed] [Google Scholar]
- Levy DE, Kessler DS, Pine R, Darnell JE., Jr Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro. Genes Dev. 1989 Sep;3(9):1362–1371. [PubMed] [Google Scholar]
- Dale TC, Imam AM, Kerr IM, Stark GR. Rapid activation by interferon alpha of a latent DNA-binding protein present in the cytoplasm of untreated cells. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1203–1207. [PMC free article] [PubMed] [Google Scholar]
- Larner AC, David M, Feldman GM, Igarashi K, Hackett RH, Webb DS, Sweitzer SM, Petricoin EF, 3rd, Finbloom DS. Tyrosine phosphorylation of DNA binding proteins by multiple cytokines. Science. 1993 Sep 24;261(5129):1730–1733. [PubMed] [Google Scholar]
- Silvennoinen O, Schindler C, Schlessinger J, Levy DE. Ras-independent growth factor signaling by transcription factor tyrosine phosphorylation. Science. 1993 Sep 24;261(5129):1736–1739. [PubMed] [Google Scholar]
- Ruff-Jamison S, Chen K, Cohen S. Induction by EGF and interferon-gamma of tyrosine phosphorylated DNA binding proteins in mouse liver nuclei. Science. 1993 Sep 24;261(5129):1733–1736. [PubMed] [Google Scholar]
- Sadowski HB, Shuai K, Darnell JE, Jr, Gilman MZ. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993 Sep 24;261(5129):1739–1744. [PubMed] [Google Scholar]
- Montminy M. Trying on a new pair of SH2s. Science. 1993 Sep 24;261(5129):1694–1695. [PubMed] [Google Scholar]
- Decker T, Lew DJ, Mirkovitch J, Darnell JE., Jr Cytoplasmic activation of GAF, an IFN-gamma-regulated DNA-binding factor. EMBO J. 1991 Apr;10(4):927–932. [PMC free article] [PubMed] [Google Scholar]
- Pearse RN, Feinman R, Shuai K, Darnell JE, Jr, Ravetch JV. Interferon gamma-induced transcription of the high-affinity Fc receptor for IgG requires assembly of a complex that includes the 91-kDa subunit of transcription factor ISGF3. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4314–4318. [PMC free article] [PubMed] [Google Scholar]
- LaMarco KL, McKnight SL. Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. Genes Dev. 1989 Sep;3(9):1372–1383. [PubMed] [Google Scholar]
- Suzow J, Friedman AD. The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1). Mol Cell Biol. 1993 Apr;13(4):2141–2151. [PMC free article] [PubMed] [Google Scholar]
- Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG. Structure of the human neutrophil elastase gene. J Biol Chem. 1988 Oct 15;263(29):14739–14747. [PubMed] [Google Scholar]
- Skalnik DG, Strauss EC, Orkin SH. CCAAT displacement protein as a repressor of the myelomonocytic-specific gp91-phox gene promoter. J Biol Chem. 1991 Sep 5;266(25):16736–16744. [PubMed] [Google Scholar]
- Alcalay M, Antolini F, Van de Ven WJ, Lanfrancone L, Grignani F, Pelicci PG. Characterization of human and mouse c-fes cDNA clones and identification of the 5' end of the gene. Oncogene. 1990 Mar;5(3):267–275. [PubMed] [Google Scholar]
- Galas DJ, Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. [PMC free article] [PubMed] [Google Scholar]
- Wright TM, Farber JM. 5' regulatory region of a novel cytokine gene mediates selective activation by interferon gamma. J Exp Med. 1991 Feb 1;173(2):417–422. [PMC free article] [PubMed] [Google Scholar]
- Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ. Genomic organization and chromosomal localization of the human cathepsin G gene. J Biol Chem. 1989 Aug 15;264(23):13412–13419. [PubMed] [Google Scholar]
- Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. [PubMed] [Google Scholar]
- Macleod K, Leprince D, Stehelin D. The ets gene family. Trends Biochem Sci. 1992 Jul;17(7):251–256. [PubMed] [Google Scholar]
- Karim FD, Urness LD, Thummel CS, Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA, Gunther CV, Nye JA, et al. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990 Sep;4(9):1451–1453. [PubMed] [Google Scholar]
- Pongubala JM, Nagulapalli S, Klemsz MJ, McKercher SR, Maki RA, Atchison ML. PU.1 recruits a second nuclear factor to a site important for immunoglobulin kappa 3' enhancer activity. Mol Cell Biol. 1992 Jan;12(1):368–378. [PMC free article] [PubMed] [Google Scholar]
- Pongubala JM, Van Beveren C, Nagulapalli S, Klemsz MJ, McKercher SR, Maki RA, Atchison ML. Effect of PU.1 phosphorylation on interaction with NF-EM5 and transcriptional activation. Science. 1993 Mar 12;259(5101):1622–1625. [PubMed] [Google Scholar]
- Eisenbeis CF, Singh H, Storb U. PU.1 is a component of a multiprotein complex which binds an essential site in the murine immunoglobulin lambda 2-4 enhancer. Mol Cell Biol. 1993 Oct;13(10):6452–6461. [PMC free article] [PubMed] [Google Scholar]
- Chen HM, Pahl HL, Scheibe RJ, Zhang DE, Tenen DG. The Sp1 transcription factor binds the CD11b promoter specifically in myeloid cells in vivo and is essential for myeloid-specific promoter activity. J Biol Chem. 1993 Apr 15;268(11):8230–8239. [PubMed] [Google Scholar]
- Hagemeier C, Bannister AJ, Cook A, Kouzarides T. The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1580–1584. [PMC free article] [PubMed] [Google Scholar]
- Zenzie-Gregory B, O'Shea-Greenfield A, Smale ST. Similar mechanisms for transcription initiation mediated through a TATA box or an initiator element. J Biol Chem. 1992 Feb 5;267(4):2823–2830. [PubMed] [Google Scholar]
- Zenzie-Gregory B, Khachi A, Garraway IP, Smale ST. 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. [PMC free article] [PubMed] [Google Scholar]
- Roy AL, Meisterernst M, Pognonec P, Roeder RG. Cooperative interaction of an initiator-binding transcription initiation factor and the helix-loop-helix activator USF. Nature. 1991 Nov 21;354(6350):245–248. [PubMed] [Google Scholar]
- Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18;67(2):377–388. [PubMed] [Google Scholar]
- Dignam JD, Martin PL, Shastry BS, Roeder RG. Eukaryotic gene transcription with purified components. Methods Enzymol. 1983;101:582–598. [PubMed] [Google Scholar]
- Lichtsteiner S, Wuarin J, Schibler U. The interplay of DNA-binding proteins on the promoter of the mouse albumin gene. Cell. 1987 Dec 24;51(6):963–973. [PubMed] [Google Scholar]
- Iyer RR. A matched set of cat vectors for rapid mutational analysis of eukaryotic promoters and enhancers. Gene. 1991 Aug 30;105(1):97–100. [PubMed] [Google Scholar]
- Zaret KS, Liu JK, DiPersio CM. Site-directed mutagenesis reveals a liver transcription factor essential for the albumin transcriptional enhancer. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5469–5473. [PMC free article] [PubMed] [Google Scholar]
- Galson DL, Hensold JO, Bishop TR, Schalling M, D'Andrea AD, Jones C, Auron PE, Housman DE. Mouse beta-globin DNA-binding protein B1 is identical to a proto-oncogene, the transcription factor Spi-1/PU.1, and is restricted in expression to hematopoietic cells and the testis. Mol Cell Biol. 1993 May;13(5):2929–2941. [PMC free article] [PubMed] [Google Scholar]
- Carvalho M, Derse D. The PU.1/Spi-1 proto-oncogene is a transcriptional regulator of a lentivirus promoter. J Virol. 1993 Jul;67(7):3885–3890. [PMC free article] [PubMed] [Google Scholar]
- Perez C, Wietzerbin J, Benech PD. Two cis-DNA elements involved in myeloid-cell-specific expression and gamma interferon (IFN-gamma) activation of the human high-affinity Fc gamma receptor gene: a novel IFN regulatory mechanism. Mol Cell Biol. 1993 Apr;13(4):2182–2192. [PMC free article] [PubMed] [Google Scholar]
- Scott LM, Civin CI, Rorth P, Friedman AD. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 1992 Oct 1;80(7):1725–1735. [PubMed] [Google Scholar]
- Mack DH, Vartikar J, Pipas JM, Laimins LA. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53. Nature. 1993 May 20;363(6426):281–283. [PubMed] [Google Scholar]
- 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. [PubMed] [Google Scholar]
- Cormack BP, Struhl K. The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells. Cell. 1992 May 15;69(4):685–696. [PubMed] [Google Scholar]
- Hernandez N. TBP, a universal eukaryotic transcription factor? Genes Dev. 1993 Jul;7(7B):1291–1308. [PubMed] [Google Scholar]
- Smale ST, Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed] [Google Scholar]
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