Sequence Analysis of the Tumor Necrosis Factor Gene in Pediatric Patients with Autoimmunity

Becker, Lisa; Brown, Torrey C.; Fink, Chester W.; Marks, James F.; Lavandosky, Gerald; Giroir, Brett P.

doi:10.1203/00006450-199502000-00007

Cited by 4 publications

(1 citation statement)

References 31 publications

(40 reference statements)

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“…The precise characterization of transcription factors binding to DNA regions essential for regulated expression of the TNF-␣ gene may open new perspectives in the understanding of human diseases related to abnormal TNF-␣ gene expression. Interestingly, mutated genomic sequences in regions flanking the 3Ј TTATTTAT signal element of TNF-␣ gene have been described in murine models (27), but not in young patients with autoimmune diseases (28). Because our results demonstrate the presence of other crucial regulatory domains interacting with promoter regions, the precise identification of discrete regulatory elements may help us to better understand the regulation of the TNF-␣ gene in inflammatory diseases.…”

Section: Tnf-␣ 3јutr Does Not Confer Toxin Inducibility Tomentioning

confidence: 69%

Human Tumor Necrosis Factor-α Gene 3′ Untranslated Region Confers Inducible Toxin Responsiveness to Homologous Promoter in Monocytic THP-1 Cells

Seiler-Tuyns

Dufour

Spertini

1999

Journal of Biological Chemistry

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To better define the role of 3 untranslated region (3UTR) on transcriptional regulation of the human tumor necrosis factor (TNF)-␣ gene, monocytic human THP-1 cells were transfected with two TNF-␣ promoter constructs spanning base pairs ؊1897/؊1 and ؊1214/؊1, respectively, and linked to the rabbit ␤-globin gene. Quantitative globin gene expression of chimerae was measured by reverse transcription-polymerase chain reaction. A construct linking the chicken ␤-actin promoter and a deleted portion of the ␤-globin gene was cotransfected and used as internal standard. Unexpectedly, when THP-1 cells were stimulated with lipopolysaccharide or toxic shock syndrome toxin-1, gene regulation was hardly detected. In contrast, endogenous TNF-␣ gene regulation measured by the same reverse transcription-polymerase chain reaction procedure was vigorous. Remarkably, ligation of 3UTR to chimeric constructs led to a drastic drop in the basal level of chimeric gene expression, resulting in a 15-to 40-fold induction of the reporter gene. Consistently, when the TNF-␣ promoter was replaced by the cytomegalovirus early immediate promoter, gene expression was also uniformly reduced but was no longer up-regulated upon stimulation with lipopolysaccharide and toxic shock syndrome toxin-1. These data provide the first line of evidence that, in addition to its role in TNF-␣ transcript stability and translation, human TNF-␣ 3UTR also participates in modulating gene expression at the transcriptional level.

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Section: Tnf-␣ 3јutr Does Not Confer Toxin Inducibility Tomentioning

confidence: 69%