Platelet-activating factor receptor. Gene structure and tissue-specific regulation.

Abstract

The human platelet-activating factor receptor gene exists as a single copy on chromosome 1. Two 5'-noncoding exons (Exon 1 and 2) has distinct transcription initiation sites and promoters. These exons are alternatively spliced to a common splice acceptor site on exon 3 that contains a total coding regions. The transcript 1 is expressed ubiquitously with an emphasis of differentiated eosinophilic cell line (Eol-1), and leukocytes. On the other hand, the transcript 2 is expressed tissue-specifically. The latter is not expressed in leukocytes or brain. The transcript 1 has three tandem repeats of NF-kappa B, and SP-1 site, and responded to various inflammatory reagents including PAF itself, lipopolysaccharide, or phorbol ester. By northern blotting of tissue or cells with various nutritional or hormonal treatments, the PAF receptor messages are up-regulated. Estrogen increased the expression of the PAF receptor in human endometrial glandular cells, and vitamin A (retinoic acid) or thyroid hormone treatment up-regulates the PAF receptor expression only tissues with transcript 2 By various in vivo and in vitro transcriptional assays (CAT reporter assay, gel mobility shift assay), we identified estrogen responsible element, and hormone responsive element. The PAF receptor hormone responsive element is composed of three direct repeated TGACCT-like hexamer motifs with 2 and 4 bp spaces, and the two upstream and two downstream motifs were identified as response elements for RA and T.