THE EXPRESSION OF THE AVIAN CLUSTERIN GENE CAN BE DRIVEN BY 2 ALTERNATIVE PROMOTERS WITH DISTINCT REGULATORY ELEMENTS

Clusterin cDNA has been isolated as a copy of a mRNA overexpressed in a wide variety of biological disorders, including tissue regression, b rain injuries and oncogenic cell transformation. While the molecular c loning of the rat and the human clusterin genes has revealed a high de gree of conservation of the genomic organization between mammals, the avian locus described here illustrates several divergent features. The avian gene has the particularity to be transcribed from at least two different promoters, both of which are active in transient expression assays using the quail QT6 transformed cell line. The detection of the two clusterin mRNA species by reverse-transcription-mediated PCR reve als a coordinated initiation of transcription from both promoters in a ll organs tested. In possible relation to the bipartite organization o f the avian regulatory region, the putative cis-elements described in the unique mammalian promoters appear divided among the two avian prom oters. In addition, the sequence comparison of avian and mammalian reg ulatory sequences has allowed the identification of a conserved putati ve cis-element which appears to be the target for specific DNA-binding factors.