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Blood, 15 June 2002, Vol. 99, No. 12, pp. 4503-4508

IMMUNOBIOLOGY

Effect of DNA methylation and chromatin structure on ITGAL expression

Qianjin Lu, Donna Ray, David Gutsch, and Bruce Richardson

From the Department of Medicine, University of Michigan; and the Ann Arbor VA Hospital; both of Ann Arbor, MI.

LFA-1 (CD11a/CD18, alpha Lbeta 2) is an integrin expressed in a tissue-specific fashion and is important in inflammatory and immune responses. Promoter analysis has identified transcription factors that may be involved in CD11a expression, but the mechanisms contributing to its tissue-specific expression are incompletely characterized. In this report we have asked if DNA methylation and/or chromatin structure could contribute to tissue-specific CD11a expression. Bisulfite sequencing was used to compare methylation patterns in the promoter and 5' flanking regions of the ITGAL gene, encoding CD11a, in normal human T cells, which express LFA-1, and fibroblasts, which do not. The region was found to be heavily methylated in fibroblasts but not T cells, and methylation correlated with an inactive chromatin configuration as analyzed by deoxyribonuclease 1 sensitivity. Patch methylation of the promoter region revealed that promoter activity was methylation-sensitive but that methylation of the 5' flanking regions more than 500 base pairs 5' to the transcription start site could also suppress promoter function. Treating fibroblasts with a DNA methylation inhibitor decreased ITGAL promoter methylation and increased CD11a messenger RNA. The results thus indicate that methylation and chromatin structure may contribute to the tissue-specific expression of CD11a.

© 2002 by The American Society of Hematology.
 

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