Immunogenetics

1432-12117562023DecImmunogeneticsImmunogeneticsThe KIR2DL1 intermediate upstream element participates in gene activation.495506495-50610.1007/s00251-023-01321-9The human KIR genes encode a family of class I MHC receptors that are expressed on subsets of NK cells. The expression of KIR proteins is controlled by a stochastic process, and competition between sense and antisense promoter elements has been suggested to program the variegated expression of these genes. Previous studies have demonstrated distinct roles of distal, intermediate, and proximal sense promoter/enhancer elements in gene activation and expression. Conversely, proximal and intronic antisense promoter transcripts have been associated with gene silencing at different stages of NK cell development. In the current study, we examine the effect of intermediate promoter deletion on KIR2DL1 expression in the YTS cell line. Homozygous deletion of the KIR2DL1 intermediate element did not affect proximal promoter activity but resulted in increased detection of upstream transcripts. No significant changes in alternative mRNA splicing or expression levels of KIR2DL1 protein were observed. However, intermediate element deletion was associated with a reduced frequency of gene activation by 5-azacytidine. Taken together, these results indicate that the intermediate element is not an enhancer required for KIR expression; however, it is required for the efficient activation of the gene.© 2023. The Author(s).WrightPaul WPWBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.LiHongchuanHBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.RahmanMd AhasanurMACancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, 21702, USA.AndersonErik MEMCancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, 21702, USA.KarwanMeganMBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.Cancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, 21702, USA.CarrellJeffreyJBasic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.Cancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, 21702, USA.AndersonStephen KSK0000-0002-7856-4266Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. andersonst@nih.gov.Cancer Innovation Laboratory, Center for Cancer Research, NCI, Frederick, MD, 21702, USA. andersonst@nih.gov.engZIA BC010013ImNIHIntramural NIH HHSUnited StatesZIA BC 010013CANCI NIH HHSUnited StatesJournal Article20231006