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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, L 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.

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