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Molecular and Cellular Biology, August 2000, p. 6051-6061, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Transcriptional Scaffold: CIITA Interacts with NF-Y, RFX, and CREB To Cause Stereospecific Regulation of the Class II Major Histocompatibility Complex Promoter

Xin-Sheng Zhu,1,2 Michael W. Linhoff,1,3 Guoxuan Li,1,3 Keh-Chuang Chin,1,4,dagger Sankar N. Maity,5 and Jenny Pan-Yun Ting1,3,*

Lineberger Comprehensive Cancer Center,1 Program in Oral Biology,2 Department of Microbiology-Immunology,3 and Department of Biochemistry and Molecular Biophysics,4 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, and Department of Molecular Genetics, M. D. Anderson Cancer Center, University of Texas, Houston, Texas 770305

Received 10 November 1999/Returned for modification 13 December 1999/Accepted 22 May 2000

Scaffold molecules interact with multiple effectors to elicit specific signal transduction pathways. CIITA, a non-DNA-binding regulator of class II major histocompatibility complex (MHC) gene transcription, may serve as a transcriptional scaffold. Regulation of the class II MHC promoter by CIITA requires strict spatial-helical arrangements of the X and Y promoter elements. The X element binds RFX (RFX5/RFXANK-RFXB/RFXAP) and CREB, while Y binds NF-Y/CBF (NF-YA, NF-YB, and NF-YC). CIITA interacts with all three. In vivo analysis using both N-terminal and C-terminal deletion constructs identified critical domains of CIITA that are required for interaction with NF-YB, NF-YC, RFX5, RFXANK/RFXB, and CREB. We propose that binding of NF-Y/CBF, RFX, and CREB by CIITA results in a macromolecular complex which allows transcription factors to interact with the class II MHC promoter in a spatially and helically constrained fashion.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-5538. Fax: (919) 966-8212. E-mail: panyun{at}med.unc.edu.

dagger Present address: Howard Hughes Medical Institute, Section of Immunology, Yale University School of Medicine, New Haven, CT 06510.

Molecular and Cellular Biology, August 2000, p. 6051-6061, Vol. 20, No. 16
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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