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

Details

Serval ID
serval:BIB_39A521193111
Type
Article: article from journal or magazin.
Collection
Publications
Title
The S box of major histocompatibility complex class II promoters is a key determinant for recruitment of the transcriptional co-activator CIITA.
Journal
The Journal of biological chemistry
Author(s)
Muhlethaler-Mottet A, Krawczyk M, Masternak K, Spilianakis C, Kretsovali A, Papamatheakis J, Reith W
Publication state
Published
Issued date
07/2004
Peer-reviewed
Oui
Language
english
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
MHC-II, CIITA, RFX, promoter, S box
Pubmed
Open Access
Yes
Create date
23/03/2020 11:44
Last modification date
24/03/2020 6:26
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