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Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I.

ABSTRACT: The type 1 interleukin-1 receptor (IL-1R1) mediates diverse functions of interleukin-1 (IL-1) in the nervous, immune, and neuroendocrine systems. It has been suggested previously that the versatile functions of IL-1 may in part be conferred by the multiple promoters of IL-1R1 that have been identified for the human IL-1R1 gene. Promoters for murine IL-1R1 (mIL-1R1) gene have not been studied in detail. We performed 5'-rapid amplification of cDNA ends to determine the transcription start sites (TSS) in mIL-1R1, using mRNAs derived from 24 different tissues. The results revealed three putative TSSs of mIL-1R1. Three full-length cDNAs containing these distinct TSSs were recovered in screens of cloned cDNA libraries. Translation of these cDNAs produced IL-1R1 proteins that were verified by Western blot analysis. IL-1 stimulation of the individual IL-1R1 proteins resulted in the activation of NF-kappaB. Promoter-reporter assay for genomic DNA sequences immediately upstream of the three TSSs validated that the sequences possess promoter activity in a cell type-specific manner. These promoters are termed P1, P2, and P3 of the mIL-1R1, in 5' to 3' order. Quantitative PCR analysis of P1-, P2-, and P3-specific mIL-1R1 mRNAs showed that there is tissue-specific distribution of these mRNAs in vivo, and there are distinct patterns of P1, P2, and P3 mRNA expression in different cell lines. In the brain, P3 mRNA is expressed preferentially in the dentate gyrus. Further, glucocorticoids differentially regulate these promoters in a cell type-specific manner. Together, these results suggest that the different IL-1R1 promoters contribute to the discrete and diverse actions of IL-1.

SUBMITTER: Chen Q

PROVIDER: S-EPMC2659229 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I.

Chen Qun Q Zhang Hao H Li Qiming Q An Ying Y Herkenham Miles M Lai Wenmin W Popovich Phillip P Agarwal Sudha S Quan Ning N

The Journal of biological chemistry 20090205 13

The type 1 interleukin-1 receptor (IL-1R1) mediates diverse functions of interleukin-1 (IL-1) in the nervous, immune, and neuroendocrine systems. It has been suggested previously that the versatile functions of IL-1 may in part be conferred by the multiple promoters of IL-1R1 that have been identified for the human IL-1R1 gene. Promoters for murine IL-1R1 (mIL-1R1) gene have not been studied in detail. We performed 5'-rapid amplification of cDNA ends to determine the transcription start sites (T ...[more]

PMID: 19196714

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Project description:Transcriptome diversity provides the key to cellular identity. One important contribution to expression diversity is the use of alternative promoters, which creates mRNA isoforms by expanding the choice of transcription initiation sites of a gene. The proximity of the basal promoter to the transcription initiation site enables prediction of a promoter's location based on the gene annotations. We show that annotation of alternative promoters regulating expression of transcripts with distinct first exons enables a novel methodology to quantify expression levels and tissue specificity of mRNA isoforms.The use of distinct alternative first exons in 3,296 genes was examined using exon-microarray data from 11 human tissues. Comparing two transcripts from each gene we found that the activity of alternative promoters (i.e., P1 and P2) was not correlated through tissue specificity or level of expression. Furthermore neither P1 nor P2 conferred any bias for tissue-specific or ubiquitous expression. Genes associated with specific diseases produced transcripts whose limited expression patterns were consistent with the tissue affected in disease. Notably, genes that were historically designated as tissue-specific or housekeeping had alternative isoforms that showed differential expression. Furthermore, only a small number of alternative promoters showed expression exclusive to a single tissue indicating that "tissue preference" provides a better description of promoter activity than tissue specificity. When compared to gene expression data in public databases, as few as 22% of the genes had detailed information for more than one isoform, whereas the remainder collapsed the expression patterns from individual transcripts into one profile.We describe a computational pipeline that uses microarray data to assess the level of expression and breadth of tissue profiles for transcripts with distinct first exons regulated by alternative promoters. We conclude that alternative promoters provide individualized regulation that is confirmed through expression levels, tissue preference and chromatin modifications. Although the selective use of alternative promoters often goes uncharacterized in gene expression analyses, transcripts produced in this manner make unique contributions to the cell that requires further exploration.

Dataset Information

Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I.

Publications

Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I.

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