期刊
JOURNAL OF IMMUNOLOGY
卷 175, 期 2, 页码 1030-1040出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.2.1030
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资金
- NIGMS NIH HHS [GM 47310, T32 GM008490] Funding Source: Medline
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 trim-ethylation, distinguished the very active HLA-DPA 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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