A Functionally Essential Domain of RFX5 Mediates Activation of Major Histocompatibility Complex Class II Promoters by Promoting Cooperative Binding between RFX and NF-Y

doi:10.1128/MCB.20.10.3364-3376.2000

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Villard, J.
	Articles by Reith, W.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Villard, J.
	Articles by Reith, W.

Molecular and Cellular Biology, May 2000, p. 3364-3376, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

A Functionally Essential Domain of RFX5 Mediates Activation of Major Histocompatibility Complex Class II Promoters by Promoting Cooperative Binding between RFX and NF-Y

Jean Villard,¹^,^* Marie Peretti,¹ Krzysztof Masternak,¹ Emmanuèle Barras,¹ Giuseppina Caretti,² Roberto Mantovani,² and Walter Reith¹^,^*

Department of Genetics and Microbiology, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland,¹ and Dipartimento di Genetica e di Biologia dei Microorganismi, Università di Milano, Milan 20133, Italy²

Received 24 September 1999/Returned for modification 23 November 1999/Accepted 18 February 2000

Major histocompatibility complex class II (MHC-II) molecules occupy a pivotal position in the adaptive immune system, andcorrect regulation of their expression is therefore of criticalimportance for the control of the immune response. Several regulatoryfactors essential for the transcription of MHC-II genes have beenidentified by elucidation of the molecular defects responsiblefor MHC-II deficiency, a hereditary immunodeficiency disease characterizedby regulatory defects abrogating MHC-II expression. Three of thesefactors, RFX5, RFXAP, and RFXANK, combine to form the RFX complex,a regulatory protein that binds to the X box DNA sequence presentin all MHC-II promoters. In this study we have undertaken a dissectionof the structure and function of RFX5, the largest subunit ofthe RFX complex. The results define two distinct domains servingtwo different essential functions. A highly conserved N-terminalregion of RFX5 is required for its association with RFXANK andRFXAP, for assembly of the RFX complex in vivo and in vitro, andfor binding of this complex to its X box target site in the MHC-IIpromoter. This N-terminal region is, however, not sufficient foractivation of MHC-II expression. This requires an additional domainwithin the C-terminal region of RFX5. This C-terminal domain mediatescooperative binding between the RFX complex and NF-Y, a transcriptionfactor binding to the Y box sequence of MHC-II promoters. Thisprovides direct evidence that RFX5-mediated cooperative bindingbetween RFX and NF-Y plays an essential role in the transcriptionalactivation of MHC-IIgenes.

^* Corresponding author. Mailing address for Jean Villard and Walter Reith: Department of Genetics and Microbiology, Universityof Geneva Medical School, CMU, 1 rue Michel-Servet, CH-1211 Geneva4, Switzerland. Phone for Jean Villard: (41 22) 702 56 72. Phonefor Walter Reith: (41 22) 702 56 66. Fax for both correspondingauthors: (41 22) 702 57 02. E-mail for Jean Villard: Jean.Villard{at}medecine.unige.ch.E-mail for Walter Reith: Walter.Reith{at}medecine.unige.ch.

Molecular and Cellular Biology, May 2000, p. 3364-3376, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Krawczyk, M., Leimgruber, E., Seguin-Estevez, Q., Dunand-Sauthier, I., Barras, E., Reith, W. (2007). Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes. Nucleic Acids Res 35: 595-605 [Abstract] [Full Text]
Niesen, M. I., Osborne, A. R., Yang, H., Rastogi, S., Chellappan, S., Cheng, J. Q., Boss, J. M., Blanck, G. (2005). Activation of a Methylated Promoter Mediated by a Sequence-specific DNA-binding Protein, RFX. J. Biol. Chem. 280: 38914-38922 [Abstract] [Full Text]
Kabe, Y., Yamada, J., Uga, H., Yamaguchi, Y., Wada, T., Handa, H. (2005). NF-Y Is Essential for the Recruitment of RNA Polymerase II and Inducible Transcription of Several CCAAT Box-Containing Genes. Mol. Cell. Biol. 25: 512-522 [Abstract] [Full Text]
Osborne, A. R., Zhang, H., Fejer, G., Palubin, K. M., Niesen, M. I., Blanck, G. (2004). 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. 279: 28911-28919 [Abstract] [Full Text]
Challacombe, J. F., Rechtsteiner, A., Gottardo, R., Rocha, L. M., Browne, E. P., Shenk, T., Altherr, M. R., Brettin, T. S. (2004). Evaluation of the host transcriptional response to human cytomegalovirus infection. Physiol. Genomics 18: 51-62 [Abstract] [Full Text]
Jabrane-Ferrat, N., Nekrep, N., Tosi, G., Esserman, L. J., Peterlin, B. M. (2002). 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. 22: 5616-5625 [Abstract] [Full Text]
Sengupta, P. K., Fargo, J., Smith, B. D. (2002). The RFX Family Interacts at the Collagen (COL1A2) Start Site and Represses Transcription. J. Biol. Chem. 277: 24926-24937 [Abstract] [Full Text]
Shao, L., Sperber, K. (2002). Impaired Regulation of HLA-DR Expression in Human Immunodeficiency Virus-Infected Monocytes. CVI 9: 739-746 [Full Text]
Morotomi-Yano, K., Yano, K.-i., Saito, H., Sun, Z., Iwama, A., Miki, Y. (2002). Human Regulatory Factor X 4 (RFX4) Is a Testis-specific Dimeric DNA-binding Protein That Cooperates with Other Human RFX Members. J. Biol. Chem. 277: 836-842 [Abstract] [Full Text]
Liberati, C., Cera, M. R., Secco, P., Santoro, C., Mantovani, R., Ottolenghi, S., Ronchi, A. (2001). Cooperation and Competition between the Binding of COUP-TFII and NF-Y on Human epsilon - and gamma -Globin Gene Promoters. J. Biol. Chem. 276: 41700-41709 [Abstract] [Full Text]
Gobin, S. J. P., van Zutphen, M., Westerheide, S. D., Boss, J. M., van den Elsen, P. J. (2001). The MHC-Specific Enhanceosome and Its Role in MHC Class I and {beta}2-Microglobulin Gene Transactivation. J. Immunol. 167: 5175-5184 [Abstract] [Full Text]
Peretti, M., Villard, J., Barras, E., Zufferey, M., Reith, W. (2001). Expression of the Three Human Major Histocompatibility Complex Class II Isotypes Exhibits a Differential Dependence on the Transcription Factor RFXAP. Mol. Cell. Biol. 21: 5699-5709 [Abstract] [Full Text]
Sisk, T. J., Roys, S., Chang, C.-H. (2001). Self-Association of CIITA and Its Transactivation Potential. Mol. Cell. Biol. 21: 4919-4928 [Abstract] [Full Text]
Vereshchagina, L. A., Tolnay, M., Tsokos, G. C. (2001). Multiple Transcription Factors Regulate the Inducible Expression of the Human Complement Receptor 2 Promoter. J. Immunol. 166: 6156-6163 [Abstract] [Full Text]
Lennon-Dumenil, A.-M., Barbouche, M.-R., Vedrenne, J., Prod'Homme, T., Bejaoui, M., Ghariani, S., Charron, D., Fellous, M., Dellagi, K., Alcaide-Loridan, C. (2001). Uncoordinated HLA-D Gene Expression in a RFXANK-Defective Patient with MHC Class II Deficiency. J. Immunol. 166: 5681-5687 [Abstract] [Full Text]
Harton, J. A., Ting, J. P.-Y. (2000). Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression. Mol. Cell. Biol. 20: 6185-6194 [Full Text]

J. Bacteriol.	J. Virol.	Eukaryot. Cell

Microbiol. Mol. Biol. Rev.	Clin. Vaccine Immunol.	All ASM Journals