CIITA and the MHCII Enhanceosome in the Regulation of MHCII Expression

Details

Serval ID
serval:BIB_2CF800D62920
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
CIITA and the MHCII Enhanceosome in the Regulation of MHCII Expression
Journal
Current Genomics
Author(s)
Landmann S, Waldburger JM, Masternak K, Muhlethaler-Mottet A, Reith W
ISSN
1389-2029
Publication state
Published
Issued date
01/05/2003
Peer-reviewed
Oui
Language
english
Abstract
Major Histocompatibility Complex class II (MHCII) molecules direct the development, activation and homeostasis of CD4+ T cells. Given these key functions it is not surprising that the absence of MHCII expression results in a severe primary immunodeficiency disease called MHCII deficiency or the Bare Lymphocyte Syndrome (BLS). The genetic defects responsible for BLS lie in genes encoding transcription factors required for MHCII expression. Four different MHCII regulatory genes encoding RFXANK, RFX5, RFXAP and CIITA have been identified. The first three are subunits of RFX, a ubiquitously expressed factor that binds cooperatively with other proteins to MHCII and related promoters to form a highly stable macromolecular nucleoprotein complex referred to as the MHCII enhanceosome. This enhanceosome serves as a landing pad for the MHCII transactivator CIITA. CIITA is a non-DNA binding coactivator that serves as the master control factor for MHCII expression. The highly regulated expression pattern of CIITA ultimately dictates the cell type specificity, induction and level of MHCII expression. The enhanceosome and CIITA collaborate in activating transcription by promoting histone hyperacetylation and by recruiting components of the general transcription machinery. In this review we summarize what is known about the molecular basis of BLS and what this has taught us about the mechanisms regulating transcription of MHCII and related genes. Particular attention is devoted to the structure, function and mode of action of the MHCII enhanceosome and CIITA. In addition, we focus on the highly regulated and cell type specific expression of CIITA.
Keywords
MHC-II Enhanceosome, CIITA, hyperacetylation, histone, immunodeficiency disease, Bare Lymphocyte
Create date
23/03/2020 11:44
Last modification date
24/03/2020 11:50
Usage data