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CIITA and the MHCII enhanceosome in the regulation of MHCII expression


LeibundGut-Landmann, Salomé; Waldburger, J; Masternak, K; Muhlethaler-Mottet, A; Reith, W (2003). CIITA and the MHCII enhanceosome in the regulation of MHCII expression. Current genomics, 4(4):343-363.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Genetics
Health Sciences > Genetics (clinical)
Language:English
Date:1 May 2003
Deposited On:03 Jul 2019 10:34
Last Modified:31 Jul 2020 03:27
Publisher:Bentham Science Publishers Ltd.
ISSN:1389-2029
OA Status:Closed
Publisher DOI:https://doi.org/10.2174/1389202033490330

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