Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-1beta is produced primarily by activated monocytes/macrophages. We report in this study that IL-1beta induces the human pro-IL-1beta (IL1B) gene promoter in human THP-1 monocytic cells. The -131 to +12 minimal IL1B promoter was induced by IL-1beta in a dose-dependent manner. The promoter possesses two important transcription factor binding motifs, one for an ETS family transcription factor Spi-1 (PU.1), and the other a binding site for NF-IL6 (CCAAT/enhancer binding protein beta). Autocrine promoter activity was completely inhibited by mutation of the Spi-1 site. Mutation of the NF-IL6 binding motif caused partial loss of activity. EMSAs using THP-1 cell nuclear extracts indicated that IL-1beta significantly induced Spi-1 binding to its target site within the IL1B promoter that was maximal at 1 h after stimulation, correlating with the kinetics of IL-1beta induction. The importance of Spi-1 was supported by our observation that Spi-1-deficient EL4 thymocytes exhibited IL-1beta-induced activity only after transfection with a Spi-1 expression vector. Moreover, TNFR-associated factor 6 also required Spi-1 to activate the promoter. Transfection studies using Spi-1 mutant constructs showed that the TATA-binding protein binding and glutamine-rich domains of Spi-1 were important for IL-1beta induction, whereas LPS induction required the proline, glutamic acid, serine, and threonine-rich domain containing serine 148 as well as the TATA-binding protein and glutamine-rich domains. We conclude that the IL1B promoter is an IL-1beta-responsive sequence as a result of its ability to bind Spi-1 in response to IL-1beta.
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PMID:Autocrine induction of the human pro-IL-1beta gene promoter by IL-1beta in monocytes. 1182 35

In the genome of eukaryotic organisms, each protein-coding gene has the unique promoter in the 5'-flanking region, and the direction of the promoter is usually controlled unidirectional. In this study, we revealed that the intergenic region between TATA-box binding protein (tbp) and proteasome subunit C3 (psmc3) genes in Medaka functions as bidirectional promoter in vitro and in vivo. The tbp and psmc3 genes were allocated as a head-to-head configuration with a 719bp intergenic region. A comparative analysis of gene arrangement surrounding loci of tbp in vertebrates also illustrated that it was unique in Acanthopterygii lineage. The transcription activities were about 1.2 times for tbp direction and 0.7 times for psmc3 direction against that of SV40 promoter in Medaka fibroblasts, respectively. A dual fluorescent reporter assay directly showed that the bidirectional promoter could express two divergent genes concurrently without disruption of RNA polymerase II elongation. In addition, an analysis of sequential deletion of this promoter suggested that the ETS binding site was necessary for maximum expression of downstream gene, and only the ETS binding site was shared from fish to mammals. In mammals, high correlation with CpG islands was observed in such bidirectional promoters, no association was found in the tbp/psmc3 bidirectional promoter in Medaka. These results suggest that molecular machineries of fish bidirectional promoter may be somehow different from those of mammals but the cis-acting element for binding ETS transcription factors is essential for divergent gene expression.
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PMID:Intergenic region between TATA-box binding protein and proteasome subunit C3 genes of Medaka function as the bidirectional promoter in vitro and in vivo. 2302 19