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IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes.
J Immunol. 1999 Apr 15; 162(8):4731-9.JI

Abstract

The transcriptional activation of class II MHC genes requires the class II transactivator (CIITA) protein, a regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The CIITA gene is controlled by multiple independent promoters; two promoters direct constitutive expression, while another, the type IV CIITA promoter, mediates IFN-gamma-induced expression. We investigated the molecular regulation of IFN-gamma-induced type IV CIITA promoter activity in astrocytes. IFN-gamma inducibility of the type IV CIITA promoter is dependent on three cis-acting elements contained within a 154-bp fragment of the promoter; the proximal IFN-gamma activation sequence (GAS) element, the E box, and the proximal IFN regulatory factor (IRF) element. Two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the proximal GAS and IRF elements, respectively. The E box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Furthermore, STAT-1alpha binding to the proximal GAS element is dependent on the binding of USF-1 to the adjacent E box. Functionally, the proximal IRF element is essential for IFN-gamma induction of type IV CIITA promoter activity, while the proximal GAS and E box elements contribute to the IFN-gamma inducibility of this promoter. In astrocytes, TNF-alpha enhances IFN-gamma-induced class II MHC transcription. Our results demonstrate that TNF-alpha does not enhance IFN-gamma-induced transcriptional activation of the type IV CIITA promoter, indicating that the enhancing effect of TNF-alpha is mediated downstream of CIITA transcription. These results define the molecular basis of IFN-gamma activation of the type IV CIITA promoter in astrocytes.

Authors+Show Affiliations

Department of Cell Biology, University of Alabama, Birmingham 35294, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10202014

Citation

Dong, Y, et al. "IFN-gamma Regulation of the Type IV Class II Transactivator Promoter in Astrocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 8, 1999, pp. 4731-9.
Dong Y, Rohn WM, Benveniste EN. IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes. J Immunol. 1999;162(8):4731-9.
Dong, Y., Rohn, W. M., & Benveniste, E. N. (1999). IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes. Journal of Immunology (Baltimore, Md. : 1950), 162(8), 4731-9.
Dong Y, Rohn WM, Benveniste EN. IFN-gamma Regulation of the Type IV Class II Transactivator Promoter in Astrocytes. J Immunol. 1999 Apr 15;162(8):4731-9. PubMed PMID: 10202014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IFN-gamma regulation of the type IV class II transactivator promoter in astrocytes. AU - Dong,Y, AU - Rohn,W M, AU - Benveniste,E N, PY - 1999/4/14/pubmed PY - 1999/4/14/medline PY - 1999/4/14/entrez SP - 4731 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 162 IS - 8 N2 - The transcriptional activation of class II MHC genes requires the class II transactivator (CIITA) protein, a regulator that is essential for both constitutive and IFN-gamma-inducible class II MHC expression. The CIITA gene is controlled by multiple independent promoters; two promoters direct constitutive expression, while another, the type IV CIITA promoter, mediates IFN-gamma-induced expression. We investigated the molecular regulation of IFN-gamma-induced type IV CIITA promoter activity in astrocytes. IFN-gamma inducibility of the type IV CIITA promoter is dependent on three cis-acting elements contained within a 154-bp fragment of the promoter; the proximal IFN-gamma activation sequence (GAS) element, the E box, and the proximal IFN regulatory factor (IRF) element. Two IFN-gamma-activated transcription factors, STAT-1alpha and IRF-1, bind the proximal GAS and IRF elements, respectively. The E box binds upstream stimulating factor-1 (USF-1), a constitutively expressed transcription factor. Furthermore, STAT-1alpha binding to the proximal GAS element is dependent on the binding of USF-1 to the adjacent E box. Functionally, the proximal IRF element is essential for IFN-gamma induction of type IV CIITA promoter activity, while the proximal GAS and E box elements contribute to the IFN-gamma inducibility of this promoter. In astrocytes, TNF-alpha enhances IFN-gamma-induced class II MHC transcription. Our results demonstrate that TNF-alpha does not enhance IFN-gamma-induced transcriptional activation of the type IV CIITA promoter, indicating that the enhancing effect of TNF-alpha is mediated downstream of CIITA transcription. These results define the molecular basis of IFN-gamma activation of the type IV CIITA promoter in astrocytes. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10202014/IFN_gamma_regulation_of_the_type_IV_class_II_transactivator_promoter_in_astrocytes_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10202014 DB - PRIME DP - Unbound Medicine ER -