Identification and analysis of the human CD160 promoter: implication of a potential AML-1 binding site in promoter activation

Abstract

CD160 is a glycosylphosphatidylinositol-anchored multimer expressed at the cell surface of subsets of cytotoxic T-lymphocytes and natural killer cells. Although CD160 is an important molecule for the control of cell-mediated cytotoxic responses, the mechanisms of regulation of its expression is unknown. We investigated the regulation of CD160 transcription by localizing and analyzing its promoter. The CD160 gene is encoded on chromosome 1, contains 6 exons with the translation initiation codon in exon 3. Bioinformatics analysis pointed to three potential promoter regions, two upstream of exon 1 and one in front of exon 3. RACE-PCR analysis identified a single transcription start site (TSS) and reporter gene transfections localized the active region immediately upstream of exon 1. Sequential deletion analysis led to the identification of a 371 bp sequence, located between À314 and þ 57 relative to the TSS, as the core promoter sequence driving CD160 gene transcription. Sequence alignment of the mouse and human CD160 genomic promoter region revealed a strong homology in the 371 bp sequence identified and pointed out to three conserved transcription factor binding sites for acute myelogenous leukemia-1 (AML-1), FREAC-4 and Sox17. Site-directed mutagenesis showed that the predicted AML-1 site is essential for the regulation of CD160 gene expression.

Combination of CD160 and CD200 as a useful tool for differential diagnosis between chronic lymphocytic leukemia and other mature B‐cell neoplasms

“…It can be recognized by two distinct monoclonal antibodies (mAbs), BY55, and CL1‐R2 . The CD160 gene is located on chromosome 1 and contains 6 exons . This 80‐kD cell surface protein is expressed by circulating natural killer (NK) cells, most γ/δ T‐cell receptor (TCR) expressing lymphocytes and a subset of CD3 + CD8 + T lymphocytes.…”

Regulation of IFN-λ1 Promoter Activity (IFN-λ1/IL-29) in Human Airway Epithelial Cells

“…Studies of promoter function continue to shed light on the role of immune-system components in health and disease (27)(28)(29)(30). To begin to explore the nature of IFN-l1 production by airway epithelial cells, we characterized the regulation of IFN-l1 transcription in a model of human airway viral infection.…”

CD160 receptor in CLL: Current state and future avenues

“…Its gene is located on the human 1q21.1 chromosome. It contains 6 exons, with exons 1 and 2 being untranslated ( 56 ) ( Figure 1 ). A core promoter sequence containing a single transcription start site (TSS) is located upstream of exon 1 ( 56 ).…”

“…It contains 6 exons, with exons 1 and 2 being untranslated ( 56 ) ( Figure 1 ). A core promoter sequence containing a single transcription start site (TSS) is located upstream of exon 1 ( 56 ). This sequence is homologous to three highly conserved transcription factor-binding sites for FREAC-4, SOX17, and acute myelogenous leukemia-1 (AML-1) (also called RUNX1 or CBFα).…”