Genes in a 220-kb Region Spanning the TNF Cluster in Human MHC

Nalabolu, Srinivasa; Shukla, Hridayabhiranjan; Nallur, Girish; Parimoo, Satish; Weissman, Sherman M.

doi:10.1006/geno.1996.0034

Cited by 35 publications

(18 citation statements)

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“…lung, tonsil, thymus, placenta, kidney, spleen, and liver). However, a high level of LST1 mRNA was detected only in macrophage and monocytic cell lines (3,6). The previous RT-PCR data from our group showed that the expression pattern of the LST1 gene in U937 cells was similar to that found in human monocytic and dentridic cells derived from human blood (data not shown).…”

Section: Discussionsupporting

confidence: 65%

“…The leukocyte-specific transcript 1 (LST1) 1 gene, the human homologue of the mouse B144 transcript, is located within 15 kilobases upstream of the tumor necrosis factor cluster in the major histocompatibility complex class IV region, a region that contains a number of genes that may play a role in various aspects of stress, inflammation, and immune responses (1)(2)(3)(4)(5)(6)(7)(8).…”

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Characterization of the Promoter of Human Leukocyte-specific Transcript 1

Weissman²

2000

Journal of Biological Chemistry

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The gene for the human leukocyte-specific transcript 1 (LST1) encodes a small protein that modulates immune responses and cellular morphogenesis. The LST1 transcripts are expressed at high levels in dendritic cells. Because of the complex splicing pattern, use of alternative 5-untranslated exons, and a biologically interesting pattern of expression of LST1 mRNA, we studied the human LST1 gene promoter and regulatory elements. We identified an additional upstream 5-untranslated exon in U937 monocytic cells. Transient transfection studies demonstrated that the combination of regions from ؊1363 to ؊621 with ؊112 to ؊54, relative to the translation start codon, produced the highest level of transcripts from among the various constructs tested, but the pattern of transcripts produced was only a subset of those produced from the endogenous gene. DNase I footprinting analysis and electrophoretic mobility shift assays showed that oligonucleotide probes corresponding to three regions, ؊1171 to ؊1142 (BI), ؊1136 to ؊1111 (BII), and ؊783 to ؊751 (BIV), bound proteins in U937 nuclear extracts. Competition and supershift electrophoretic mobility shift assay did not identify any known transcription factors responsible for BII probe binding. These studies suggest that a novel DNA-binding site and interaction of multiple regulatory elements may be involved in mediating the expression of the various forms of LST1 mRNA.The leukocyte-specific transcript 1 (LST1) 1 gene, the human homologue of the mouse B144 transcript, is located within 15 kilobases upstream of the tumor necrosis factor cluster in the major histocompatibility complex class IV region, a region that contains a number of genes that may play a role in various aspects of stress, inflammation, and immune responses (1-8).The human LST1 mRNA is most actively transcribed in monocytes and dendritic cells, and its mRNA levels can be enhanced by interferon (IFN)-␥, suggesting a role of LST1 in the immune response (9 -12). A recent study showed that this gene product had an inhibitory effect on lymphocyte proliferation (13). Transient transfection studies in our laboratory showed that the LST1 gene product induced extensive thin cytoplasmic extensions in a wide variety of cells in vitro and, in particular, was strongly expressed in dendritic cells in vivo and in vitro. 2Due to alternative splicing, the LST1 gene in human and mouse encodes multiple transcripts, each 800 nucleotides or less in length. Previous studies on the human LST1 gene showed that this gene consisted of at least eight exons and four introns, including four different alternative 5Ј-UT exons (termed 1A, 1B, 1C, and 1D, respectively) and four additional exons spanning 2.7 kilobases. The extensive alternative splicing of LST1 mRNA results in high structural diversity of the putative encoded polypeptides (9). The DNA sequences between these 5Ј-UT exons do not consistently show sequence features resembling promoters.There are certain unusual features of the relationship between the human LST1 mRNA and the gene se...

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Section: Discussionsupporting

confidence: 65%

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confidence: 99%

Characterization of the Promoter of Human Leukocyte-specific Transcript 1

Weissman²

2000

Journal of Biological Chemistry

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“…24,25 Northern blot analysis confirmed that expression of these genes was induced in PU.1-1 cells treated with ZnCl 2 for 48 hours ( Figure 1, lane 11). In cells treated with both DMSO and ZnCl 2 , levels of expression of these genes were lower than in cells treated with ZnCl 2 alone ( Figure 1, lanes 11 and 12).…”

Section: Identification Of Genes In Mel Cells Whose Expression Changementioning

confidence: 67%

Lineage switch induced by overexpression of Ets family transcription factor PU.1 in murine erythroleukemia cells

Yamada

Abe

Higashi

et al. 2001

Blood

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PU.1 is an Ets family transcription factor essential for myelomonocyte and B-cell development. We previously showed that overexpression of PU.1 in murine erythroleukemia (MEL) cells inhibits growth and erythroid differentiation and induces apoptosis of the cells. In an effort to identify target genes of PU.1 concerning these phenomena by using a messenger RNA differential display strategy, we found that some myeloid-specific and lymphoidspecific genes, such as the osteopontin gene, are transcriptionally up-regulated in MEL cells after overexpression of PU.1. We then found that expression of several myelomonocyte-specific genes, including the CAAT-enhancer-binding protein-␣ and granulocyte-macrophage colonystimulating factor receptor genes, was induced in MEL cells after overexpression of PU.1. B-cell-specific genes were also examined, and expression of the CD19 gene was found to be induced.

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“…These include the major histocompatibility complex class I chain (MIC)-related genes MICA 8 and MICB, 10 and members of the UL16-binding proteins (ULBP)/retinoic acid early transcript 1 (RAET1) gene family. 10,11 Both the MIC genes (located on chromosome 6p21.3 12,13 ) and ULBP/RAET1 genes (positioned at 6q25 10 ) encode stress-inducible protein products, upregulated in malignant and virally infected cells and constitutively expressed within the epithelium of the gut. 10,11,14,15 The MIC-restricted Vd1 subset of gd T cells are the predominant lymphocyte present within intestinal epithelium.…”

Section: Introductionmentioning

confidence: 99%

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

et al. 2006

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Killer immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and some T-cell subsets and produce either activation or inhibitory signals upon binding with the appropriate human leucocyte antigen (HLA) ligand on target cells. Recent genetic association studies have implicated KIR genotype in the development of several inflammatory conditions. Ulcerative colitis (UC) is an inflammatory disorder of the colonic mucosa that results from an inappropriate activation of the immune system driven by host bacterial flora. We developed a polymerase chain reaction-sequence specific primer (SSP)-based assay to genotype 194 UC patients and 216 control individuals for 14 KIR genes, the HLA-Cw ligand epitopes of the KIR2D receptors and a polymorphism of the lectin-like-activating receptor NKG2D. Initial analysis found the phenotype frequency of KIR2DL2 and -2DS2 to be significantly increased in the UC cohort (P ¼ 0.030 and 0.038, respectively). Logistic regression analysis revealed a protective effect conferred by KIR2DL3 in the presence of its ligand HLA-Cw group 1 (P ¼ 0.019). These results suggest that KIR genotype and HLA ligand interaction may contribute to the genetic susceptibility of UC.

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Genes in a 220-kb Region Spanning the TNF Cluster in Human MHC

Cited by 35 publications

References 0 publications

Characterization of the Promoter of Human Leukocyte-specific Transcript 1

Characterization of the Promoter of Human Leukocyte-specific Transcript 1

Lineage switch induced by overexpression of Ets family transcription factor PU.1 in murine erythroleukemia cells

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

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