Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus
dc.contributor.author | Lu, Qianjin | en_US |
dc.contributor.author | Kaplan, Mariana J. | en_US |
dc.contributor.author | Ray, Donna | en_US |
dc.contributor.author | Ray, Doreen | en_US |
dc.contributor.author | Zacharek, Sima | en_US |
dc.contributor.author | Gutsch, David | en_US |
dc.contributor.author | Richardson, Bruce C. | en_US |
dc.date.accessioned | 2006-04-19T13:27:26Z | |
dc.date.available | 2006-04-19T13:27:26Z | |
dc.date.issued | 2002-05 | en_US |
dc.identifier.citation | Lu, Qianjin; Kaplan, Mariana; Ray, Donna; Ray, Doreen; Zacharek, Sima; Gutsch, David; Richardson, Bruce (2002)."Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus." Arthritis & Rheumatism 46(5): 1282-1291. <http://hdl.handle.net/2027.42/34301> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/34301 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=12115234&dopt=citation | en_US |
dc.description.abstract | Objective Inhibition of T cell DNA methylation causes autoreactivity in vitro and a lupus-like disease in vivo, suggesting that T cell DNA hypomethylation may contribute to autoimmunity. The hypomethylation effects are due, in part, to overexpression of lymphocyte function–associated antigen 1 (LFA-1) (CD11a/CD18). Importantly, T cells from patients with active lupus have hypomethylated DNA and overexpress LFA-1 on an autoreactive subset, suggesting that the same mechanism could contribute to human lupus. The present study investigated the nature of the methylation change that affects LFA-1 expression in vitro and in human lupus. Methods Bisulfite sequencing was used to determine the methylation status of the ITGAL promoter and flanking regions in T cells from lupus patients and healthy subjects, and in T cells treated with DNA methylation inhibitors. “Patch” methylation of promoter sequences in reporter constructs was used to determine the functional significance of the methylation changes. Results Hypomethylation of specific sequences flanking the ITGAL promoter was seen in T cells from patients with active lupus and in T cells treated with 5-azacytidine and procainamide. Patch methylation of this region suppressed ITGAL promoter function. Conclusion DNA methylation changes occur in specific sequences that regulate LFA-1 expression in lupus T cells and in the hypomethylation model, indicating that altered methylation of specific genes may play a role in the pathogenesis of lupus. | en_US |
dc.format.extent | 342094 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor ; 5310 Cancer Center and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109-0940 | en_US |
dc.contributor.affiliationother | Vanderbilt University, Nashville, Tennessee | en_US |
dc.contributor.affiliationother | University of North Carolina, Chapel Hill | en_US |
dc.contributor.affiliationother | Merck, Whitehouse Station, New Jersey | en_US |
dc.identifier.pmid | 12115234 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/34301/1/10234_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.10234 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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