Identification of Upstream cis-Acting Regulatory Elements Controlling Lineage-specific Expression of the Mouse NK Cell Activation Receptor, NKR-P1C

Ljutic, Belma; Carlyle, James R.; Zúñiga‐Pflücker, Juan Carlos

doi:10.1074/jbc.m212869200

Cited by 11 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The distal promoter of some Ly-49 genes was shown to have promoter activity in fetal cells and in bone marrow cells, possibly linking its usage to the initiation of Ly-49 expression in NK cells (55). In addition, the mouse NKR-P1C gene has also recently been shown to have a novel upstream noncoding exon that is differentially used during NK cell development, as well as a DNase I HSS upstream of the gene (35). It is very interesting that many NK receptor genes, at least in mice, share several common characteristics, including alternative first exons whose use varies during development as well as the presence of DNase I HSS, although this has not yet been demonstrated to occur in the case of Ly-49 genes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Wilhelm

Landry

Takei

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

The CD94 gene product is involved in controlling NK cell activation, and is one of a family of immune receptors that is found in the NK gene complex in both humans and mice, adjacent to members of the NKG2 family. CD94 forms a heterodimeric complex with several members of the NKG2 family on the surface of NK, T, and NKT cells. These complexes recognize the nonclassical MHC class I molecules HLA-E and Qa-1b in humans and mice, respectively. The mechanism for cell type-specific expression of CD94 and other genes from the NK gene complex has not yet been elucidated. In the current study, we show that the murine CD94 gene has two promoters, one of which is upstream of a previously unidentified exon. We illustrate by quantitative real-time PCR that lymphoid cell types use these two promoters differentially and that the promoter usage seen in adult cells is already established during fetal development. We determined that the differential promoter usage by NK cells appears to be susceptible to perturbation, as both the murine NK cell line LNK, as well as cultured C57BL/6 NK cells showed altered promoter usage relative to fresh NK cells. Furthermore, the promoter activity observed in transfection assays did not correlate with expression of the endogenous CD94 gene, suggesting the involvement of chromatin structure/methylation in transcriptional regulation. Our detection of DNase I hypersensitive sites at the CD94 locus that are present only in a cell line expressing endogenous CD94 supports this hypothesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Wilhelm

Landry

Takei

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

Section: Structurementioning

confidence: 99%

“…There were early attempts to analyze the upstream regions of the mouse Nkrp1 genes in different strains (49, 111). The proximal promoters appear to be TATA-less, relying on initiator (Inr) and downstream promoter elements (DPE) (111). The mouse Nkrp1 genes also appear to possess a three-promoter organization similar to that seen for the mouse Ly49 genes (112).…”

Section: Structurementioning

confidence: 99%

“…The mouse Nkrp1 genes also appear to possess a three-promoter organization similar to that seen for the mouse Ly49 genes (112). Several predicted transcription factor-binding sites in the distal and proximal promoter regions are speculated to be important in regulating Nkrp1 expression, including consensus Ets-1, Ikaros, GATA, TCF-1, Sp1, NFAT, and Oct-1 sites (111). In addition, a number of upstream regulatory elements have been mapped, including transcriptional start sites (TSS), alternative exons, and a distal DNase hypersensitive site that may function as an enhancer element.…”

Section: Structurementioning

confidence: 99%

See 1 more Smart Citation

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Kirkham

Carlyle

2014

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

The NKR-P1 receptors were identified as prototypical natural killer (NK) cell surface antigens and later shown to be conserved from rodents to humans on NK cells and subsets of T cells. C-type lectin-like in nature, they were originally shown to be capable of activating NK cell function and to recognize ligands on tumor cells. However, certain family members have subsequently been shown to be capable of inhibiting NK cell activity, and to recognize proteins encoded by a family of genetically linked C-type lectin-related ligands. Some of these ligands are expressed by normal, healthy cells, and modulated during transformation, infection, and cellular stress, while other ligands are upregulated during the immune response and during pathological circumstances. Here, we discuss historical and recent developments in NKR-P1 biology that demonstrate this NK receptor–ligand system to be far more complex and diverse than originally anticipated.

show abstract

“…al. (39) to conform to the Ly49 gene nomenclature (i.e., exon 2, cytoplasmic; exon 3, transmembrane, exon 4, stalk; exons 5-7, C-type lectin-like domain).…”

Section: Conformational Nature Of the Nk11 Epitopementioning

confidence: 99%

Molecular and Genetic Basis for Strain-Dependent NK1.1 Alloreactivity of Mouse NK Cells

Carlyle

Mesci

Ljutic

et al. 2006

The Journal of Immunology

Self Cite

117

112

View full text Add to dashboard Cite

NK1.1 alloantigen expression can be used to define NK cells in certain mouse strains, such as B6 (NKR-P1C) and SJL (NKR-P1B). However, BALB/c NK cells do not react with the anti-NK1.1 mAb, PK136. To investigate the NK1.1− phenotype of BALB/c NK cells, we have undertaken NK1.1 epitope mapping and genomic analysis of the BALB/c Nkrp1 region. Bacterial artificial chromosome library analysis reveals that, unlike the Ly49 region, the Nkrp1-Ocil/Clr region displays limited genetic divergence between B6 and BALB/c mice. In fact, significant divergence is confined to the Nkrp1b and Nkrp1c genes. Strikingly, the B6 Nkrp1d gene appears to represent a divergent allele of the Nkrp1b gene in BALB/c mice and other strains. Importantly, BALB/c NK cells express abundant and functional Nkrp1 transcripts, and the BALB/c NKR-P1B receptor functionally binds Ocil/Clr-b ligand. However, the BALB/c NKR-P1B/C sequences differ from those of the known NK1.1 alloantigens, and epitope mapping demonstrates that directed mutation of a single amino acid in the NKR-P1BBALB protein confers NK1.1 reactivity. Thus, PK136 mAb recognizes, in part, a distal C-terminal epitope present in NKR-P1BSw/SJL and NKR-P1CB6, but absent in NKR-P1A/D/FB6 and NKR-P1B/CBALB. Allelic divergence of the Nkrp1b/c gene products and limited divergence of the BALB/c Nkrp1-Ocil/Clr region explain a longstanding confusion regarding the strain-specific NK1.1 alloantigen reactivity of mouse NK cells.

show abstract

Identification of Upstream cis-Acting Regulatory Elements Controlling Lineage-specific Expression of the Mouse NK Cell Activation Receptor, NKR-P1C

Abstract: The classic NK1

Cited by 11 publications

References 32 publications

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Transcriptional Control of MurineCD94Gene: Differential Usage of Dual Promoters by Lymphoid Cell Types

Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems

Molecular and Genetic Basis for Strain-Dependent NK1.1 Alloreactivity of Mouse NK Cells

Contact Info

Product

Resources

About