Effect of DNA methylation and chromatin structure onITGAL expression
Open Access
- 15 June 2002
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 99 (12), 4503-4508
- https://doi.org/10.1182/blood.v99.12.4503
Abstract
LFA-1 (CD11a/CD18, αLβ2) 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.Keywords
This publication has 28 references indexed in Scilit:
- Molecular Mechanisms Mediating Methylation-Dependent Silencing of Ribosomal Gene TranscriptionMolecular Cell, 2001
- Methylation-Induced Repression— Belts, Braces, and ChromatinCell, 1999
- Mapping Patterns of CpG Island Methylation in Normal and Neoplastic Cells Implicates Both Upstream and Downstream Regions inde Novo MethylationPublished by Elsevier BV ,1997
- Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice.JCI Insight, 1996
- Cell Adhesion Molecules CD11a and CD18 in Blood Monocytes in Old Age and the Consequences for Immunological DysfunctionGerontology, 1995
- Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosusArthritis & Rheumatism, 1992
- Methylation-Sensitive Sequence-Specific DNA Binding by the c-Myc Basic RegionScience, 1991
- CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation.Genes & Development, 1989
- Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion.The Journal of Experimental Medicine, 1988
- Increased immunoglobulin response to γ-interferon by lymphocytes from patients with systemic lupus erythematosusClinical Immunology and Immunopathology, 1988