Abstract
The mechanism of transcriptional activation of human leukocyte antigen class I genes by gamma interferon and 5-azacytidine was studied in K562 human leukemia cells. Nuclear run-on transcription assays with various protein and RNA synthesis inhibitors yield evidence for both stimulation of a positive regulatory factor and inhibition of an mRNA that codes for a labile repressor. A novel mechanism is proposed to explain how 5-azacytidine can activate repressed genes without affecting DNA methylation.
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Selected References
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- Baglioni C., Maroney P. A. Mechanisms of action of human interferons. Induction of 2'5'-oligo(A) polymerase. J Biol Chem. 1980 Sep 25;255(18):8390–8393. [PubMed] [Google Scholar]
- Baldacci P., Transy C., Cochet M., Penit C., Israel A., Kourilsky P. A trans-acting mechanism represses the expression of the major transplantation antigens in mouse hybrid thymoma cell lines. J Exp Med. 1986 Sep 1;164(3):677–694. doi: 10.1084/jem.164.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
- Breslow J. L., Ross D., McPherson J., Williams H., Kurnit D., Nussbaum A. L., Karathanasis S. K., Zannis V. I. Isolation and characterization of cDNA clones for human apolipoprotein A-I. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6861–6865. doi: 10.1073/pnas.79.22.6861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen E., Karr R. W., Frost J. P., Gonwa T. A., Ginder G. D. Gamma interferon and 5-azacytidine cause transcriptional elevation of class I major histocompatibility complex gene expression in K562 leukemia cells in the absence of differentiation. Mol Cell Biol. 1986 May;6(5):1698–1705. doi: 10.1128/mcb.6.5.1698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cowan E. P., Coligan J. E., Biddison W. E. Human cytotoxic T-lymphocyte recognition of an HLA-A3 gene product expressed on murine L cells: the only human gene product required on the target cells for lysis is the class I heavy chain. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4490–4494. doi: 10.1073/pnas.82.13.4490. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davidson W. F., Kress M., Khoury G., Jay G. Comparison of HLA class I gene sequences. Derivation of locus-specific oligonucleotide probes specific for HLA-A, HLA-B, and HLA-C genes. J Biol Chem. 1985 Nov 5;260(25):13414–13423. [PubMed] [Google Scholar]
- Doyle A., Martin W. J., Funa K., Gazdar A., Carney D., Martin S. E., Linnoila I., Cuttitta F., Mulshine J., Bunn P. Markedly decreased expression of class I histocompatibility antigens, protein, and mRNA in human small-cell lung cancer. J Exp Med. 1985 May 1;161(5):1135–1151. doi: 10.1084/jem.161.5.1135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
- Gomard E., Begue B., Sodoyer S., Maryanski J. L., Jordan B. R., Levy J. P. Murine cells expressing an HLA molecule are specifically lysed by HLA-restricted antiviral human T cells. Nature. 1986 Jan 9;319(6049):153–154. doi: 10.1038/319153a0. [DOI] [PubMed] [Google Scholar]
- Goodenow R. S., Vogel J. M., Linsk R. L. Histocompatibility antigens on murine tumors. Science. 1985 Nov 15;230(4727):777–783. doi: 10.1126/science.2997918. [DOI] [PubMed] [Google Scholar]
- Hayashi H., Tanaka K., Jay F., Khoury G., Jay G. Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon. Cell. 1985 Nov;43(1):263–267. doi: 10.1016/0092-8674(85)90031-5. [DOI] [PubMed] [Google Scholar]
- Hui K., Grosveld F., Festenstein H. Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984 Oct 25;311(5988):750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
- Jones P. A. Altering gene expression with 5-azacytidine. Cell. 1985 Mar;40(3):485–486. doi: 10.1016/0092-8674(85)90192-8. [DOI] [PubMed] [Google Scholar]
- Jones P. A., Taylor S. M. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980 May;20(1):85–93. doi: 10.1016/0092-8674(80)90237-8. [DOI] [PubMed] [Google Scholar]
- Kufe D. W., Major P. P., Egan E. M., Beardsley G. P. Correlation of cytotoxicity with incorporation of ara-C into DNA. J Biol Chem. 1980 Oct 10;255(19):8997–8900. [PubMed] [Google Scholar]
- Lampson L. A., Fisher C. A., Whelan J. P. Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines. J Immunol. 1983 May;130(5):2471–2478. [PubMed] [Google Scholar]
- Larner A. C., Jonak G., Cheng Y. S., Korant B., Knight E., Darnell J. E., Jr Transcriptional induction of two genes in human cells by beta interferon. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733–6737. doi: 10.1073/pnas.81.21.6733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lozzio C. B., Lozzio B. B. Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome. Blood. 1975 Mar;45(3):321–334. [PubMed] [Google Scholar]
- Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
- McClelland M., Nelson M. The effect of site specific methylation on restriction endonuclease digestion. Nucleic Acids Res. 1985;13 (Suppl):r201–r207. doi: 10.1093/nar/13.suppl.r201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyazaki J., Appella E., Ozato K. Negative regulation of the major histocompatibility class I gene in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9537–9541. doi: 10.1073/pnas.83.24.9537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pfizenmaier K., Bartsch H., Scheurich P., Seliger B., Ucer U., Vehmeyer K., Nagel G. A. Differential gamma-interferon response of human colon carcinoma cells: inhibition of proliferation and modulation of immunogenicity as independent effects of gamma-interferon on tumor cell growth. Cancer Res. 1985 Aug;45(8):3503–3509. [PubMed] [Google Scholar]
- Razin A., Szyf M., Kafri T., Roll M., Giloh H., Scarpa S., Carotti D., Cantoni G. L. Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc Natl Acad Sci U S A. 1986 May;83(9):2827–2831. doi: 10.1073/pnas.83.9.2827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg S. A., Spiess P., Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986 Sep 19;233(4770):1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
- Sood A. K., Pereira D., Weissman S. M. Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981 Jan;78(1):616–620. doi: 10.1073/pnas.78.1.616. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sutherland J., Mannoni P., Rosa F., Huyat D., Turner A. R., Fellous M. Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate. Hum Immunol. 1985 Feb;12(2):65–73. doi: 10.1016/0198-8859(85)90344-1. [DOI] [PubMed] [Google Scholar]
- Tamm I., Sehgal P. B. Halobenzimidazole ribosides and RNA synthesis of cells and viruses. Adv Virus Res. 1978;22:187–258. doi: 10.1016/s0065-3527(08)60775-7. [DOI] [PubMed] [Google Scholar]
- Tanaka K., Isselbacher K. J., Khoury G., Jay G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985 Apr 5;228(4695):26–30. doi: 10.1126/science.3975631. [DOI] [PubMed] [Google Scholar]
- Travers P. J., Arklie J. L., Trowsdale J., Patillo R. A., Bodmer W. F. Lack of expression of HLA-ABC antigens in choriocarcinoma and other human tumor cell lines. Natl Cancer Inst Monogr. 1982;60:175–180. [PubMed] [Google Scholar]
- Vasavada R., Eager K. B., Barbanti-Brodano G., Caputo A., Ricciardi R. P. Adenovirus type 12 early region 1A proteins repress class I HLA expression in transformed human cells. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5257–5261. doi: 10.1073/pnas.83.14.5257. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veselý J. Mode of action and effects of 5-azacytidine and of its derivatives in eukaryotic cells. Pharmacol Ther. 1985;28(2):227–235. doi: 10.1016/0163-7258(85)90012-9. [DOI] [PubMed] [Google Scholar]
- Wallach D., Fellous M., Revel M. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982 Oct 28;299(5886):833–836. doi: 10.1038/299833a0. [DOI] [PubMed] [Google Scholar]
- Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]