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6724840 
Journal Article 
DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors 
Liu, Y; Kuick, R; Hanash, S; Richardson, B; , 
2009 
Yes 
Clinical Immunology
ISSN: 1521-6616
EISSN: 1521-7035 
ACADEMIC PRESS INC ELSEVIER SCIENCE 
SAN DIEGO 
213-224 
18945643 
WOS:000262882800010 
Killer-cell immunoglobulin-like receptor (KIR) genes are a polymorphic family expressed on NK cells, and "senescent" CD28-T cells implicated in cardiovascular disease. KIR promoters are highly homologous, and NK expression is regulated by DNA methylation. T cell. KIR regulation is poorly understood. We asked if epigenetic mechanisms and/or transcription factor alterations determine T cell KIR expression. DNA methylation inhibition activated multiple KIR genes in normal T cells. KIR2DL2 and KIR2DL4 were selected for further study. Expression of both was associated with promoter demethylation, and methylation of the promoters in reporter constructs suppressed expression. KIR reporter construct expression also increased in demethylated T cells and required Ets1, Sp1 and AML sites, implying effects on transcription factors. This was confirmed for Sp1. These results indicate that KIR genes are suppressed by DNA methylation in most T cells, and DNA demethylation promotes their expression through effects on both chromatin structure and transcription factors. Published by Elsevier Inc.