This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morris, A. C.
Right arrow Articles by Boss, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morris, A. C.
Right arrow Articles by Boss, J. M.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2002, p. 4781-4791, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4781-4791.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Kinetics of a Gamma Interferon Response: Expression and Assembly of CIITA Promoter IV and Inhibition by Methylation

Ann C. Morris, Guy W. Beresford, Myesha R. Mooney, and Jeremy M. Boss*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 23 October 2001/ Returned for modification 3 December 2001/ Accepted 28 March 2002

Chromatin immunoprecipitation assays were employed to assess the kinetics of transcription factor assembly and histone modifications that occur during gamma interferon (IFN-{gamma}) induction of CIITA gene expression. CIITA is the master regulator of major histocompatibility complex class II transcription. Promoter IV (PIV), the major IFN-{gamma} responsive promoter for CIITA expression, requires both STAT1 and IFN regulatory factor 1 (IRF-1) for induction by IFN-{gamma}. STAT1 binding to PIV was detected first and was accompanied by a modest acetylation of histones H3 and H4 that were associated with the region. Despite these changes, which occurred within 30 min of IFN-{gamma} treatment, CIITA mRNA was not detected until IRF-1 protein was synthesized and bound to its site, a process that required >120 min. In contrast to these events, fetal trophoblast-like cell lines, which are refractory to CIITA induction by IFN-{gamma}, failed to assemble the above factors or modify their chromatin, suggesting that accessibility to the promoter is blocked. Bisulfite sequencing of PIV showed strong hypermethylation of PIV, providing a link between methylation, chromatin structure, and factor binding. Together, this analysis provides a kinetic view of the activation of the CIITA gene in response to IFN-{gamma} and shows that regulatory factor assembly, chromatin modification, and gene expression proceed in discrete steps.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-5973. Fax: (404) 727-1719. E-mail: boss{at}microbio.emory.edu.

Molecular and Cellular Biology, July 2002, p. 4781-4791, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4781-4791.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koues, O. I., Dudley, R. K., Truax, A. D., Gerhardt, D., Bhat, K. P., McNeal, S., Greer, S. F. (2008). Regulation of Acetylation at the Major Histocompatibility Complex Class II Proximal Promoter by the 19S Proteasomal ATPase Sug1. Mol. Cell. Biol. 28: 5837-5850 [Abstract] [Full Text]  
  • Holling, T. M., Bergevoet, M. W. T., Wilson, L., Van Eggermond, M. C. J. A., Schooten, E., Steenbergen, R. D. M., Snijders, P. J. F., Jager, M. J., Van den Elsen, P. J. (2007). A Role for EZH2 in Silencing of IFN-{gamma} Inducible MHC2TA Transcription in Uveal Melanoma. J. Immunol. 179: 5317-5325 [Abstract] [Full Text]  
  • Zhao, W., Cha, E. N., Lee, C., Park, C. Y., Schindler, C. (2007). Stat2-Dependent Regulation of MHC Class II Expression. J. Immunol. 179: 463-471 [Abstract] [Full Text]  
  • Ramsauer, K., Farlik, M., Zupkovitz, G., Seiser, C., Kroger, A., Hauser, H., Decker, T. (2007). Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-{gamma}-inducible gbp2 gene. Proc. Natl. Acad. Sci. USA 104: 2849-2854 [Abstract] [Full Text]  
  • Choi, J. C., Holtz, R., Petroff, M. G., Alfaidy, N., Murphy, S. P. (2007). Dampening of IFN-{gamma}-Inducible Gene Expression in Human Choriocarcinoma Cells Is Due to Phosphatase-Mediated Inhibition of the JAK/STAT-1 Pathway. J. Immunol. 178: 1598-1607 [Abstract] [Full Text]  
  • Sanda, T., Iida, S., Kayukawa, S., Ueda, R. (2007). Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. haematol 92: 115-120 [Abstract] [Full Text]  
  • Tooze, R. M., Stephenson, S., Doody, G. M. (2006). Repression of IFN-{gamma} Induction of Class II Transactivator: A Role for PRDM1/Blimp-1 in Regulation of Cytokine Signaling. J. Immunol. 177: 4584-4593 [Abstract] [Full Text]  
  • Yao, Y., Xu, Q., Kwon, M.-J., Matta, R., Liu, Y., Hong, S.-C., Chang, C.-H. (2006). ERK and p38 MAPK Signaling Pathways Negatively Regulate CIITA Gene Expression in Dendritic Cells and Macrophages. J. Immunol. 177: 70-76 [Abstract] [Full Text]  
  • Pennini, M. E., Pai, R. K., Schultz, D. C., Boom, W. H., Harding, C. V. (2006). Mycobacterium tuberculosis 19-kDa Lipoprotein Inhibits IFN-{gamma}-Induced Chromatin Remodeling of MHC2TA by TLR2 and MAPK Signaling. J. Immunol. 176: 4323-4330 [Abstract] [Full Text]  
  • Ni, Z., Karaskov, E., Yu, T., Callaghan, S. M., Der, S., Park, D. S., Xu, Z., Pattenden, S. G., Bremner, R. (2005). Apical role for BRG1 in cytokine-induced promoter assembly. Proc. Natl. Acad. Sci. USA 102: 14611-14616 [Abstract] [Full Text]  
  • Roy, S. K., Shuman, J. D., Platanias, L. C., Shapiro, P. S., Reddy, S. P. M., Johnson, P. F., Kalvakolanu, D. V. (2005). A Role for Mixed Lineage Kinases in Regulating Transcription Factor CCAAT/Enhancer-binding Protein-{beta}-dependent Gene Expression in Response to Interferon-{gamma}. J. Biol. Chem. 280: 24462-24471 [Abstract] [Full Text]  
  • Meng, Q., Raha, A., Roy, S., Hu, J., Kalvakolanu, D. V. (2005). IFN-{gamma}-Stimulated Transcriptional Activation by IFN-{gamma}-Activated Transcriptional Element-Binding Factor 1 Occurs via an Inducible Interaction with CAAAT/Enhancer-Binding Protein-{beta}. J. Immunol. 174: 6203-6211 [Abstract] [Full Text]  
  • Goriely, S., Van Lint, C., Dadkhah, R., Libin, M., De Wit, D., Demonte, D., Willems, F., Goldman, M. (2004). A Defect in Nucleosome Remodeling Prevents IL-12(p35) Gene Transcription in Neonatal Dendritic Cells. JEM 199: 1011-1016 [Abstract] [Full Text]  
  • O'Sullivan, A., Chang, H.-C., Yu, Q., Kaplan, M. H. (2004). STAT4 Is Required for Interleukin-12-induced Chromatin Remodeling of the CD25 Locus. J. Biol. Chem. 279: 7339-7345 [Abstract] [Full Text]  
  • Eivazova, E. R., Aune, T. M. (2004). Dynamic alterations in the conformation of the Ifng gene region during T helper cell differentiation. Proc. Natl. Acad. Sci. USA 101: 251-256 [Abstract] [Full Text]  
  • Popkin, D. L., Watson, M. A., Karaskov, E., Dunn, G. P., Bremner, R., Virgin, H. W. IV (2003). Murine cytomegalovirus paralyzes macrophages by blocking IFN{gamma}-induced promoter assembly. Proc. Natl. Acad. Sci. USA 100: 14309-14314 [Abstract] [Full Text]  
  • Holtz, R., Choi, J. C., Petroff, M. G., Piskurich, J. F., Murphy, S. P. (2003). Class II Transactivator (CIITA) Promoter Methylation Does Not Correlate with Silencing of CIITA Transcription in Trophoblasts. Biol. Reprod. 69: 915-924 [Abstract] [Full Text]  
  • Pai, R. K., Convery, M., Hamilton, T. A., Boom, W. H., Harding, C. V. (2003). Inhibition of IFN-{gamma}-Induced Class II Transactivator Expression by a 19-kDa Lipoprotein from Mycobacterium tuberculosis: A Potential Mechanism for Immune Evasion. J. Immunol. 171: 175-184 [Abstract] [Full Text]  
  • Kanaseki, T., Ikeda, H., Takamura, Y., Toyota, M., Hirohashi, Y., Tokino, T., Himi, T., Sato, N. (2003). Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas. J. Immunol. 170: 4980-4985 [Abstract] [Full Text]  
  • Moreau, P., Mouillot, G., Rousseau, P., Marcou, C., Dausset, J., Carosella, E. D. (2003). HLA-G gene repression is reversed by demethylation. Proc. Natl. Acad. Sci. USA 100: 1191-1196 [Abstract] [Full Text]  
  • Murphy, S. P., Holtz, R., Lewandowski, N., Tomasi, T. B., Fuji, H. (2002). DNA Alkylating Agents Alleviate Silencing of Class II Transactivator Gene Expression in L1210 Lymphoma Cells. J. Immunol. 169: 3085-3093 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»