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The S box of major histocompatibility complex class II promoters is a key determinant for recruitment of the transcriptional co-activator CIITA

Muhlethaler-Mottet, Annick
Spilianakis, Charalambos
Kretsovali, Androniki
Papamatheakis, Joseph
Published in Journal of Biological Chemistry. 2004, vol. 279, no. 39, p. 40529-40535
Abstract Tightly regulated expression of major histocompatibility complex (MHC) class II genes is critical for the immune system. A conserved regulatory module consisting of four cis-acting elements, the W, X, X2 and Y boxes, controls transcription of MHC class II genes. The X, X2, and Y boxes are bound, respectively, by RFX, CREB, and NF-Y to form a MHC class II-specific enhanceosome complex. The latter constitutes a landing pad for recruitment of the transcriptional co-activator CIITA. In contrast to the well defined roles of the X, X2, and Y boxes, the role of the W region has remained controversial. In vitro binding studies have suggested that it might contain a second RFX-binding site. We demonstrate here by means of promoter pull-down assays that the most conserved subsequence within the W region, called the S box, is a critical determinant for tethering of CIITA to the enhanceosome complex. Binding of CIITA to the enhanceosome requires both integrity of the S box and a remarkably stringent spacing between the S and X boxes. Even a 1-2-base pair change in the native S-X distance is detrimental for CIITA recruitment and promoter function. In contrast to current models, binding of RFX to a putative duplicated binding site in the W box is thus not required for either CIITA recruitment or promoter activity. This paves the way for the identification of novel factors mediating the contribution of the S box to the activation of MHC class II promoters.
Keywords Base SequenceBinding SitesCell LineGenes, MHC Class IIHumansImmunoblottingLuciferases/metabolismMajor Histocompatibility ComplexMolecular Sequence DataMutationNuclear Proteins/ geneticsPromoter Regions, GeneticProtein BindingTrans-Activators/ geneticsTranscription, GeneticTranscriptional Activation
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PMID: 15271997

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Deposited on : 2010-08-27

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