![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 14, No. 9, pp. 1156-1166, May 1, 2000
1 Department of Genetics and Microbiology, University of
Geneva Medical School, 1211 Geneva, Switzerland; 2 Hans-Spemann-Laboratories, Max-Planck-Institute of Immunology, D-79108 Freiburg, Germany
By virtue of its control over major histocompatibility complex class
II (MHC-II) gene expression, CIITA represents a key molecule in the
regulation of adaptive immune responses. It was first identified as a
factor that is defective in MHC-II deficiency, a hereditary disease
characterized by the absence of MHC-II expression. CIITA is a highly
regulated transactivator that governs all spatial, temporal, and
quantitative aspects of MHC-II expression. It has been proposed to act
as a non-DNA-binding transcriptional coactivator, but evidence that it
actually functions at the level of MHC-II promoters was lacking. By
means of chromatin immunoprecipitation assays, we show here for the
first time that CIITA is physically associated with MHC-II, as well as
HLA-DM, Ii, MHC-I, and 
2m promoters in vivo. To dissect the mechanism by which CIITA is recruited
to the promoter, we have developed a DNA-dependent
coimmunoprecipitation assay and a pull-down assay using immobilized
promoter templates. We demonstrate that CIITA recruitment depends on
multiple, synergistic protein-protein interactions with DNA-bound
factors constituting the MHC-II enhanceosome. CIITA therefore
represents a paradigm for a novel type of regulatory and gene-specific
transcriptional cofactor.
[Key Words: MHC class II; CIITA; enhanceosome; coactivator; transcription; gene regulation]
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Xu, J. A. Harton, and B. D. Smith CIITA Mediates Interferon-{gamma} Repression of Collagen Transcription through Phosphorylation-dependent Interactions with Co-repressor Molecules J. Biol. Chem., January 18, 2008; 283(3): 1243 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. N. Bewry, S. C. E. Bolick, K. L. Wright, and J. A. Harton GTP-dependent Recruitment of CIITA to the Class II Major Histocompatibility Complex Promoter J. Biol. Chem., September 7, 2007; 282(36): 26178 - 26184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Casals, M. Barrachina, M. Serra, J. Lloberas, and A. Celada Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA J. Immunol., May 15, 2007; 178(10): 6307 - 6315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rybtsova, E. Leimgruber, Q. Seguin-Estevez, I. Dunand-Sauthier, M. Krawczyk, and W. Reith Transcription-coupled deposition of histone modifications during MHC class II gene activation Nucleic Acids Res., May 11, 2007; 35(10): 3431 - 3441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Krawczyk, E. Leimgruber, Q. Seguin-Estevez, I. Dunand-Sauthier, E. Barras, and W. Reith Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes Nucleic Acids Res., January 28, 2007; 35(2): 595 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Tooze, S. Stephenson, and G. M. Doody Repression of IFN-{gamma} Induction of Class II Transactivator: A Role for PRDM1/Blimp-1 in Regulation of Cytokine Signaling J. Immunol., October 1, 2006; 177(7): 4584 - 4593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tosi, E. Pilotti, L. Mortara, A. D. L. Barbaro, C. Casoli, and R. S. Accolla Inhibition of human T cell leukemia virus type 2 replication by the suppressive action of class II transactivator and nuclear factor Y PNAS, August 22, 2006; 103(34): 12861 - 12866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-J. Kwon, J.-W. Soh, and C.-H. Chang Protein Kinase C{delta} Is Essential to Maintain CIITA Gene Expression in B Cells J. Immunol., July 15, 2006; 177(2): 950 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yao, Q. Xu, M.-J. Kwon, R. Matta, Y. Liu, S.-C. Hong, and C.-H. Chang ERK and p38 MAPK Signaling Pathways Negatively Regulate CIITA Gene Expression in Dendritic Cells and Macrophages J. Immunol., July 1, 2006; 177(1): 70 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zika, L. Fauquier, L. Vandel, and J. P.-Y. Ting Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN-{gamma}-inducible MHC-II gene expression PNAS, November 8, 2005; 102(45): 16321 - 16326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Krawczyk, K. Masternak, M. Zufferey, E. Barras, and W. Reith New Functions of the Major Histocompatibility Complex Class II-Specific Transcription Factor RFXANK Revealed by a High-Resolution Mutagenesis Study Mol. Cell. Biol., October 1, 2005; 25(19): 8607 - 8618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Howcroft, J. D. Weissman, A. Gegonne, and D. S. Singer A T Lymphocyte-Specific Transcription Complex Containing RUNX1 Activates MHC Class I Expression J. Immunol., February 15, 2005; 174(4): 2106 - 2115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Krawczyk, N. Peyraud, N. Rybtsova, K. Masternak, P. Bucher, E. Barras, and W. Reith Long Distance Control of MHC Class II Expression by Multiple Distal Enhancers Regulated by Regulatory Factor X Complex and CIITA J. Immunol., November 15, 2004; 173(10): 6200 - 6210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Muhlethaler-Mottet, M. Krawczyk, K. Masternak, C. Spilianakis, A. Kretsovali, J. Papamatheakis, and W. Reith The S Box of Major Histocompatibility Complex Class II Promoters Is a Key Determinant for Recruitment of the Transcriptional Co-activator CIITA J. Biol. Chem., September 24, 2004; 279(39): 40529 - 40535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Osborne, H. Zhang, G. Fejer, K. M. Palubin, M. I. Niesen, and G. Blanck Oct-1 Maintains an Intermediate, Stable State of HLA-DRA Promoter Repression in Rb-defective Cells: AN Oct-1-CONTAINING REPRESSOSOME THAT PREVENTS NF-Y BINDING TO THE HLA-DRA PROMOTER J. Biol. Chem., July 9, 2004; 279(28): 28911 - 28919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Camacho-Carvajal, S. Klingler, F. Schnappauf, S. B. Hake, and V. Steimle Importance of class II transactivator leucine-rich repeats for dominant-negative function and nucleo-cytoplasmic transport Int. Immunol., January 1, 2004; 16(1): 65 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, L. Wang, G. Buttice, P. K. Sengupta, and B. D. Smith Interferon {gamma} Repression of Collagen (COL1A2) Transcription Is Mediated by the RFX5 Complex J. Biol. Chem., December 5, 2003; 278(49): 49134 - 49144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Tzortzakaki, C. Spilianakis, E. Zika, A. Kretsovali, and J. Papamatheakis Steroid Receptor Coactivator 1 Links the Steroid and Interferon {gamma} Response Pathways Mol. Endocrinol., December 1, 2003; 17(12): 2509 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Nagabhushanam, A. Solache, L.-M. Ting, C. J. Escaron, J. Y. Zhang, and J. D. Ernst Innate Inhibition of Adaptive Immunity: Mycobacterium tuberculosis-Induced IL-6 Inhibits Macrophage Responses to IFN-{gamma} J. Immunol., November 1, 2003; 171(9): 4750 - 4757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Sisk, K. Nickerson, R. P. S. Kwok, and C.-H. Chang Phosphorylation of class II transactivator regulates its interaction ability and transactivation function Int. Immunol., October 1, 2003; 15(10): 1195 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Pai, M. Convery, T. A. Hamilton, W. H. Boom, and C. V. Harding 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., July 1, 2003; 171(1): 175 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kanaseki, H. Ikeda, Y. Takamura, M. Toyota, Y. Hirohashi, T. Tokino, T. Himi, and N. Sato Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas J. Immunol., May 15, 2003; 170(10): 4980 - 4985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Zika, S. F. Greer, X.-S. Zhu, and J. P.-Y. Ting Histone Deacetylase 1/mSin3A Disrupts Gamma Interferon-Induced CIITA Function and Major Histocompatibility Complex Class II Enhanceosome Formation Mol. Cell. Biol., May 1, 2003; 23(9): 3091 - 3102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bouallaga, S. Teissier, M. Yaniv, and F. Thierry HMG-I(Y) and the CBP/p300 Coactivator Are Essential for Human Papillomavirus Type 18 Enhanceosome Transcriptional Activity Mol. Cell. Biol., April 1, 2003; 23(7): 2329 - 2340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jabrane-Ferrat, N. Nekrep, G. Tosi, L. Esserman, and B. M. Peterlin MHC class II enhanceosome: how is the class II transactivator recruited to DNA-bound activators? Int. Immunol., April 1, 2003; 15(4): 467 - 475. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Raval, J. D. Weissman, T. K. Howcroft, and D. S. Singer The GTP-Binding Domain of Class II Transactivator Regulates Its Nuclear Export J. Immunol., January 15, 2003; 170(2): 922 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. van der Stoep, E. Quinten, and P. J. van den Elsen Transcriptional Regulation of the MHC Class II Trans-Activator (CIITA) Promoter III: Identification of a Novel Regulatory Region in the 5'-Untranslated Region and an Important Role for cAMP-Responsive Element Binding Protein 1 and Activating Transcription Factor-1 in CIITA-Promoter III Transcriptional Activation in B Lymphocytes J. Immunol., November 1, 2002; 169(9): 5061 - 5071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Nagarajan, A. Bushey, and J. M. Boss Modulation of Gene Expression by the MHC Class II Transactivator J. Immunol., November 1, 2002; 169(9): 5078 - 5088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jabrane-Ferrat, N. Nekrep, G. Tosi, L. J. Esserman, and B. M. Peterlin Major Histocompatibility Complex Class II Transcriptional Platform: Assembly of Nuclear Factor Y and Regulatory Factor X (RFX) on DNA Requires RFX5 Dimers Mol. Cell. Biol., August 1, 2002; 22(15): 5616 - 5625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Pai, D. Askew, W. H. Boom, and C. V. Harding Regulation of Class II MHC Expression in APCs: Roles of Types I, III, and IV Class II Transactivator J. Immunol., August 1, 2002; 169(3): 1326 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mudhasani and J. D. Fontes The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes Mol. Cell. Biol., July 15, 2002; 22(14): 5019 - 5026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Nagarajan, J. Lochamy, X. Chen, G. W. Beresford, R. Nilsen, P. E. Jensen, and J. M. Boss Class II Transactivator Is Required for Maximal Expression of HLA-DOB in B Cells J. Immunol., February 15, 2002; 168(4): 1780 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Holling, N. van der Stoep, E. Quinten, and P. J. van den Elsen Activated Human T Cells Accomplish MHC Class II Expression Through T Cell-Specific Occupation of Class II Transactivator Promoter III J. Immunol., January 15, 2002; 168(2): 763 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Rahat, I. Chernichovski, and N. Lahat Increased binding of IFN regulating factor 1 mediates the synergistic induction of CIITA by IFN-{gamma} and tumor necrosis factor-{alpha} in human thyroid carcinoma cells Int. Immunol., November 1, 2001; 13(11): 1423 - 1432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. P. Gobin, M. van Zutphen, S. D. Westerheide, J. M. Boss, and P. J. van den Elsen The MHC-Specific Enhanceosome and Its Role in MHC Class I and {beta}2-Microglobulin Gene Transactivation J. Immunol., November 1, 2001; 167(9): 5175 - 5184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-S. Zhu and J. P.-Y. Ting A 36-Amino-Acid Region of CIITA Is an Effective Inhibitor of CBP: Novel Mechanism of Gamma Interferon-Mediated Suppression of Collagen {alpha}2(I) and Other Promoters Mol. Cell. Biol., October 15, 2001; 21(20): 7078 - 7088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Harton, E. Zika, and J. P.-Y. Ting The Histone Acetyltransferase Domains of CREB-binding Protein (CBP) and p300/CBP-associated Factor Are Not Necessary for Cooperativity with the Class II Transactivator J. Biol. Chem., October 12, 2001; 276(42): 38715 - 38720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Osborne, H. Zhang, W.-M. Yang, E. Seto, and G. Blanck Histone Deacetylase Activity Represses Gamma Interferon-Inducible HLA-DR Gene Expression following the Establishment of a DNase I-Hypersensitive Chromatin Conformation Mol. Cell. Biol., October 1, 2001; 21(19): 6495 - 6506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Cressman, W. J. O'Connor, S. F. Greer, X.-S. Zhu, and J. P.-Y. Ting Mechanisms of Nuclear Import and Export That Control the Subcellular Localization of Class II Transactivator J. Immunol., October 1, 2001; 167(7): 3626 - 3634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Peretti, J. Villard, E. Barras, M. Zufferey, and W. Reith Expression of the Three Human Major Histocompatibility Complex Class II Isotypes Exhibits a Differential Dependence on the Transcription Factor RFXAP Mol. Cell. Biol., September 1, 2001; 21(17): 5699 - 5709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Landmann, A. Muhlethaler-Mottet, L. Bernasconi, T. Suter, J.-M. Waldburger, K. Masternak, J.-F. Arrighi, C. Hauser, A. Fontana, and W. Reith Maturation of Dendritic Cells Is Accompanied by Rapid Transcriptional Silencing of Class II Transactivator (CIITA) Expression J. Exp. Med., August 13, 2001; 194(4): 379 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Sisk, S. Roys, and C.-H. Chang Self-Association of CIITA and Its Transactivation Potential Mol. Cell. Biol., August 1, 2001; 21(15): 4919 - 4928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, J. A. Harton, X. Zhu, and J. P.-Y. Ting Downregulation of CIITA Function by Protein Kinase A (PKA)-Mediated Phosphorylation: Mechanism of Prostaglandin E, Cyclic AMP, and PKA Inhibition of Class II Major Histocompatibility Complex Expression in Monocytic Lines Mol. Cell. Biol., July 15, 2001; 21(14): 4626 - 4635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kanazawa and B. M. Peterlin Combinations of dominant-negative class II transactivator, p300 or CDK9 proteins block the expression of MHC II genes Int. Immunol., July 1, 2001; 13(7): 951 - 958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Dong, L. Tang, J. J. Letterio, and E. N. Benveniste The Smad3 Protein Is Involved in TGF-{{beta}} Inhibition of Class II Transactivator and Class II MHC Expression J. Immunol., July 1, 2001; 167(1): 311 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Linhoff, J. A. Harton, D. E. Cressman, B. K. Martin, and J. P.-Y. Ting Two Distinct Domains within CIITA Mediate Self-Association: Involvement of the GTP-Binding and Leucine-Rich Repeat Domains Mol. Cell. Biol., May 1, 2001; 21(9): 3001 - 3011. [Abstract] [Full Text]
|
|
|
|
|
|
G. M. O'Keefe, V. T. Nguyen, L. Ping Tang, and E. N. Benveniste IFN-{{gamma}} Regulation of Class II Transactivator Promoter IV in Macrophages and Microglia: Involvement of the Suppressors of Cytokine Signaling-1 Protein J. Immunol., February 15, 2001; 166(4): 2260 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Hake, K. Masternak, C. Kammerbauer, C. Janzen, W. Reith, and V. Steimle CIITA Leucine-Rich Repeats Control Nuclear Localization, In Vivo Recruitment to the Major Histocompatibility Complex (MHC) Class II Enhanceosome, and MHC Class II Gene Transactivation Mol. Cell. Biol., October 15, 2000; 20(20): 7716 - 7725. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Harton and J. P.-Y. Ting Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression Mol. Cell. Biol., September 1, 2000; 20(17): 6185 - 6194. [Full Text]
|
|
|
|
|
|
A. Kretsovali, C. Spilianakis, A. Dimakopoulos, T. Makatounakis, and J. Papamatheakis Self-association of Class II Transactivator Correlates with Its Intracellular Localization and Transactivation J. Biol. Chem., August 17, 2001; 276(34): 32191 - 32197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Coustry, Q. Hu, B. de Crombrugghe, and S. N. Maity CBF/NF-Y Functions Both in Nucleosomal Disruption and Transcription Activation of the Chromatin-assembled Topoisomerase IIalpha Promoter. TRANSCRIPTION ACTIVATION BY CBF/NF-Y IN CHROMATIN IS DEPENDENT ON THE PROMOTER STRUCTURE J. Biol. Chem., October 26, 2001; 276(44): 40621 - 40630. [Abstract] [Full Text] [PDF]
|
|
