title: Regulation of CEP131 gene expression by SP1.
abstract: Centrosomal proteins play important roles in cell cycle. Among them, the centrosomal protein of 131kDa (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 -400bp and -200bp, 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.
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Republic of Korea.
authors.forename: Pham Thi Thu
authors.initials: PT
authors.lastname: Huong
authors.forename: Nak Kyun
authors.initials: NK
authors.lastname: Soung
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Cha-Molstad
authors.forename: Krisada
authors.initials: K
authors.lastname: Sakchaisri
authors.forename: Sun Ok
authors.initials: SO
authors.lastname: Kim
authors.forename: Jun Min
authors.initials: JM
authors.lastname: Jang
authors.forename: Kyoon Eon
authors.initials: KE
authors.lastname: Kim
authors.forename: Kyung Sang
authors.initials: KS
authors.lastname: Lee
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Kwon
authors.forename: Raymond Leo
authors.initials: RL
authors.lastname: Erikson
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
mesh_terms: D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D003598:Cytoskeletal Proteins; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010957:Plasmids; D008926:Plicamycin / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: C578334:CEP131 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016329:Sp1 Transcription Factor; D008926:Plicamycin