Regulation of CEP131 gene expression by SP1

Centrosomal proteins play important roles in cell cycle. Among them, the centrosomal protein of 131 kDa (CEP131) has been reported as a critical factor for cilia formation which is related with development, signaling, and various diseases, the malfunction of cilia leading to cancer. Specificity protein 1 (SP1), known as a centrosome regulator, is an essential transcription factor regulating the genes involved in multiple cellular processes such as cell cycle, apoptosis, and DNA damages. In this study, we explored the crucial role of SP1 in the regulation of CEP131 gene transcription. A deletion analysis of the CEP131 promoter region revealed dominant promoter elements within the sequence between − 400 bp and − 200 bp, which contained consensus binding sites for SP1. Electrophoretic mobility shift assay (EMSA) and chromatin immuno-precipitation (ChIP) assay further confirmed the direct binding of SP1 to the CEP131 promoter. On the other hand, CEP131 transcription could be inhibited by mithramycin (a GC-rich region inhibitor), but exogenous expression of SP1 could increase CEP131 expression as evidenced by a reporter gene assay. In addition, mutation of several SP1 binding sites revealed four SP1 binding sites at − 244/− 225, − 258/− 239, − 304/− 283 and − 323/− 304 that strongly affect CEP131 expression. Hence, it is suggested that SP1 is a pivotal transcription factor for the regulation of CEP131 expression, consequently leading the control of centrosome functions.

► SP1 binds directly on CEP131 promoter and induces CEP131 promoter activity.
► Four SP1 binding sites have compensatory function on CEP131 transcription activity.
► SP1 could be an important transcription factor regulating centrosome through CEP131.