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Review
. 2011 Feb;23(1):81-7.
doi: 10.1016/j.coi.2010.09.007. Epub 2010 Oct 21.

Regulation of major histocompatibility complex class II genes

Nancy M Choi  1 , Parimal Majumder, Jeremy M Boss
Affiliations
Review

Regulation of major histocompatibility complex class II genes

Nancy M Choi et al. Curr Opin Immunol. 2011 Feb.

Abstract

The major histocompatibility complex class II (MHC-II) genes are regulated at the level of transcription. Recent studies have shown that chromatin modification is critical for efficient transcription of these genes, and a number of chromatin modifying complexes recruited to MHC-II genes have been described. The MHC-II genes are segregated from each other by a series of chromatin elements, termed MHC-II insulators. Interactions between MHC-insulators and the promoters of MHC-II genes are mediated by the insulator factor CCCTC-binding factor and are critical for efficient expression. This regulatory mechanism provides a novel view of how the entire MHC-II locus is assembled architecturally and can be coordinately controlled.

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Conflict of interest statement

Conflicts of Interest

The authors have no financial conflict of interest with regard to this work.

Figures

Figure 1
Figure 1. MHC-II locus
Schematic of classical and non-classical MHC-II genes (black), MHC-II pseudo-genes (grey), and non-MHC-II genes (blue) together form a very gene dense locus on the short arm of human chromosome 6. The locus is punctuated with 10 CTCF binding sites (C1–C16; pink) including XL9.
Figure 2
Figure 2. Promoter proximal MHC-II regulation
Highly conserved W-X-Y box is bound by RFX, CREB, and NF-Y. They form a unique structure that is recognized by CIITA. CIITA recruits indicated transcriptional coactivators and their associated complexes that modulate the activity of the enhanceosome proteins and modify nucleosomes (ac; acetylation, me; methylation) surrounding the nucleosome free region (NFR) to regulate transcription. 19S P: 19S proteasome regulatory complex.
Figure 3
Figure 3. MHC-II insulator long-range looping model
In the ‘OFF state’, MHC-insulators bound by CTCF (orange), C1 and XL9, interact to form a chromatin loop and interaction focus. Cohesin (blue) likely encircles the interacting CTCF foci maintaining the integrity/stability of the structure or its function. When MHC-II genes are induced (ON), CIITA present at the promoters interacts with CTCF bound insulators forming a second series of interactions and sub loops. While this cartoon represents the HLA-DR subregion, additional interactions are possible with these elements [48].
See this image and copyright information in PMC

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