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CIITA coordinates multiple histone acetylation modifications at the HLA-DRA promoter

Nature Immunology volume 2, pages 652–657 (2001)Cite this article

Abstract

We present here an in vivo view of major histocompatibility complex (MHC) class II promoter assembly, nucleosome modifications and gene expression mediated by the class II transactivator (CIITA). Acetylation and deacetylation of histones H3 and H4 at the HLA-DRA promoter were found to occur during a time-course that depended on CIITA expression and binding. Expression of a CIITA mutant, which lacked the activation domain, induced H4 but not H3 histone acetylation. This suggested that multiple histone acetyltransferase activities are associated with MHC class II expression. H4 acetylation was mapped to Lys8, which implicated several histone acetyltransferases as possible modulators of this activity.

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Figure 1: CIITA binds to the class II promoter, which results in increased histone acetylation
Figure 2: Kinetics of MHC class II induction in response to IFN-γ
Figure 3: Removal of IFN-γ results in a return to basal histone acetylation
Figure 4: Multiple HAT activities are modulated by CIITA binding
Figure 5: Lys8 of H4 is preferentially hyperacetylated in both CIITA+ and CIITA− cells
Figure 6: Histone acetylation extends upstream of the HLA-DRA promoter

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Acknowledgements

We thank members of our laboratory and P. Wade and P. Jones for advice and critical comments. Supported by NIH grants GM47310 and AI34000.

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  1. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, 30322, GA, USA

    Guy W. Beresford & Jeremy M. Boss

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Correspondence to Jeremy M. Boss.

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Beresford, G., Boss, J. CIITA coordinates multiple histone acetylation modifications at the HLA-DRA promoter. Nat Immunol 2, 652–657 (2001). https://doi.org/10.1038/89810

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