XBP1 induces WFS1 through an endoplasmic reticulum stress response element-like motif in SH-SY5Y cells


Address correspondence and reprint requests to Tadafumi Kato, MD, PhD, Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. E-mail: kato@brain.riken.jp


XBP1 is a key transcription factor in the endoplasmic reticulum (ER) stress response pathway. In a previous study, we suggested a possible link between XBP1 and bipolar disorder, but its role in neuronal cells has not yet been clarified. Here we examined the target genes of XBP1, using DNA microarray analysis in SH-SY5Y cells transfected with an XBP1-expressing vector. Among the genes up-regulated by XBP1, the most significant p-value was observed for WFS1, which is an ER stress response-related gene. Examining the promoter region of WFS1, we found a conserved sequence (CGAGGCGCACCGTGATTGG) that is highly similar to the ER stress response element (ERSE). A promoter assay showed that this ERSE-like motif is critical for the regulation of WFS1 by XBP1. An electrophoretic mobility shift assay suggested that XBP1 does not directly bind to this sequence. Our results demonstrate that WFS1 is one of the target genes of XBP1 in SH-SY5Y cells.