title: Specificity protein 1 transcription factor regulates human ARTS promoter activity through multiple binding sites.
abstract: Apoptosis-related protein in the TGF-β signaling pathway (ARTS) is an unusual mitochondrial Septin-like protein which functions as a tumor suppressor. There are various splice variants derived from the human Septin4 gene, one of which is ARTS, also known as Septin4_i2. Unlike other Septin4 members, ARTS can induce apoptosis in many cells, however, the underlying molecular mechanism for the transcriptional regulation of ARTS has yet to be deciphered. In this study, we attempted to analyze the promoter region of ARTS in cultured HEK-293T and LX-2 cells with the purpose of elucidating the underlying transcriptional mechanisms driving ARTS expression. We effectively demonstrated that the -824 to -5 bp region of the ARTS promoter was essential for ARTS transcription and identified four putative specificity protein 1 (Sp1) binding sites within this core promoter region. ChIP analysis showed that Sp1 protein could bind to two of these sites (-735/-718 and -173/-157) and mutation of each Sp1 binding site led to a significant decrease in ARTS promoter activity. In conclusion, all the results indicated that the Sp1 transcription factor could contribute to ARTS gene transcription. The underlying molecular events of the specific promoter of ARTS could also be used to explain why ARTS is selectively silenced during some human diseases. This would provide basis for further study on the function of ARTS on cell apoptosis.
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China; Clinical Laboratory, The Sixth People's Hospital of Nantong, Nantong 226001, Jiangsu, People's Republic of China.
authors: Feifan
authors: F
authors: Xu
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Wei
authors: W
authors: Sun
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Pan
authors: P
authors: Li
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Jinling
authors: J
authors: Chen
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Dandan
authors: D
authors: Zhu
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Xiaolei
authors: X
authors: Sun
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China; Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, People's Republic of China.
authors: Jianxin
authors: J
authors: Wang
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Jinrong
authors: J
authors: Feng
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Ke
authors: K
authors: Song
authors: Department of Pathogen Biology, School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu, People's Republic of China.
authors: Yinong
authors: Y
authors: Duan
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D058112:Septins / Q000737:chemistry / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
chemical_list: D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C492027:SEPTIN4 protein, human; D058112:Septins