Clusterin gene in rat Sertoli cells is regulated by a core-enhancer element

Clusterin is a ubiquitous glycoprotein that is promiscuously expressed at a low basal level but can be highly induced by a variety of stress condition s. In contrast, in some secretory cells associated with tissue-fluid interf aces such as the Sertoli cells in the testis, clusterin demonstrates high c onstitutive expression. In this study, we address the mechanisms that regul ate the constitutive expression of the clusterin gene by using primary cult ures of immature rat Sertoli cells. We have identified a region of the rat clusterin gene promoter that activated transcription only in Sertoli cells and that mapped between positions -426 and -311. Sequence analysis of this region revealed a high concentration of potential regulatory elements. Usin g gel-shift assays combined with hydroxyl radical footprinting, we identifi ed the elements recognized by the Sertoli cell nuclear factors. Comparison of the interactions with this region of the nuclear factors from different cell types demonstrated that recognition of the core-enhancer element is sp ecific for the Sertoli cells, and in vitro, the core region was recognized by the transcription factor CBF. Transient transfections showed that a core enhancer is responsible for more than a half of the total promoter activit y and is an essential element for the cell-specific activity of the Sertoli -specific region. In addition to the core enhancer, tandem Spl sites are al so required for maximal activity of this region.