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The Journal of Immunology, 2005, 175: 1030-1040.
Copyright © 2005 by The American Association of Immunologists

X Box-Like Sequences in the MHC Class II Region Maintain Regulatory Function1

Jorge A. Gomez, Parimal Majumder, Uma M. Nagarajan2 and Jeremy M. Boss3

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

Sequences homologous to the canonical MHC class II (MHC-II) gene X box regulatory elements were identified within the HLA-DR subregion of the human MHC and termed X box-like (XL) sequences. Several XL box sequences were found to bind the MHC class II-specific transcription factors regulatory factor X and CIITA and were transcriptionally active. The histone code associated with the XL boxes and that of the HLA-DRA X box was determined. Using CIITA-positive and -negative B cell lines, CIITA-specific histone modifications were identified and found to be consistent among the active XL boxes. Although a remarkable similarity was observed for most modifications, differences in magnitude between the HLA-DRA promoter for modifications associated with the assembly of the general transcription factors, such as histone H3 lysine 9 acetylation and H3 lysine 4 trimethylation, distinguished the very active HLA-DRA promoter from the XL box regions. In response to IFN-{gamma}, XL box-containing histones displayed increased acetylation, coincident with CIITA expression and that observed in B cells, suggesting that the end point mechanisms of chromatin remodeling for cell type-specific MHC-II expression were similar. Lastly, an interaction between one XL box and the HLA-DRA promoter was observed in a chromatin-looping assay. Therefore, these data provide evidence that certain XL box sequences contribute to a global increase in chromatin accessibility of the HLA-DR region in B lymphocytes and in response to IFN-{gamma} and supports the involvement of these XL sequences in the regulation of MHC-II genes.




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