
-   Ionizing radiation increases CLU promoter activity in cultured cancer cells, an effect mediated via EGR-1 and EGR-1 consensus sites. Radiation exposure caused stress-induced activation of IGF-1R-Src-Mek-Erk-Egr-1 signaling that regulates the secretory clusterin protein (sCLU) pro-survival cascade pathway, important for radiation resistance in cancer therapy [PMID: 15689620].
-   TGF-beta regulates clusterin gene expression through an AP-1 site and its cognate transcription factor AP-1, and requires the involvement of protein kinase C [PMID: 9334243].
-   In primary cultures of immature rat Sertoli cells, a region of the rat clusterin gene promoter was identified that activated transcription only in Sertoli cells. This core-enhancer element is specific for the Sertoli cells, and in vitro, the core region was recognized by the transcription factor CBF. Transient transfections showed that this core enhancer is responsible for more than a half of the total promoter activity and is an essential element for the cell-specific activity of the Sertoli-specific region. In addition to the core enhancer, tandem Sp1 sites are also required for maximal activity of this region [PMID: 11058537].
-   Both clusterin protein and mRNA levels increased in response to proteasome inhibitor treatment in the human glial cell line U-251MG. Chromatin-immunoprecipitation experiments showed that an upstream DNA region of CLU was bound by HSF1 (heat-shock factor 1) and HSF2 upon proteasome inhibition [PMID: 16336210]. Another study showed that the only DNA region strictly conserved between clusterin gene proximal promoters from different vertebrate classes is specifically recognized by the HSF1 transcription factor and can mediate heat-shock-induced transcription in transient expression assays [PMID: 9359832].
-   In U2OS osteosarcoma cell line and the WI38 primary human embryonic lung fibroblasts, results indicates that CLU overexpression after proteasome inhibition relates to both positive gene transcriptional regulation by HSF-1 and posttranslational protein accumulation due to reduced proteasomal and lysosomal degradation [PMID: 19353783].
-   CLU promoter was found to be hypomethylated in DNA from blood and lens capsules of Pseudoexfoliation (PEX) patients compared to controls that correlated with decreased expression of DNA methyltransferase 1 (DNMT1). Promoter demethylation of CLU using DNMT inhibitor, 5'-aza-dC, in human lens epithelial cells increased CLU expression. Chromatin immunoprecipitation assays showed that the demethylated CLU promoter provides increased access to the transcription factor, Sp1, which might lead to enhanced expression of CLU [PMID: 37652361].
