title: Sp sites contribute to basal and inducible expression of the human TNIP1 (TNFα-inducible protein 3-interacting protein 1) promoter.
abstract: TNIP1 [TNFα (tumour necrosis factor α)-induced protein 3-interacting protein 1] is a co-repressor of RAR (retinoic acid receptor) and PPAR (peroxisome-proliferator-activated receptor). Additionally, it can reduce signalling stemming from cell membrane receptors such as those for TNFα and EGF (epidermal growth factor). Consequently, it influences a variety of receptor-mediated events as diverse as transcription, programmed cell death and cell cycling. Thus changes in TNIP1 expression levels are likely to affect multiple important biological end points. TNIP1 expression level changes have been linked to psoriasis and systemic sclerosis. As such, it is crucial to determine what controls its expression levels, starting with constitutive control of its promoter. Our analysis of the TNIP1 promoter revealed multiple transcription start sites in its GC-rich proximal regions along with two transcriptionally active Sp (specificity protein) sites, responsive to both Sp1 and Sp3. EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation) demonstrated physical binding between Sp1 and Sp3 at these sites. A decrease in Sp1 protein levels via siRNA (short interfering RNA) or diminished Sp1 DNA binding by mithramycin decreased TNIP1 mRNA levels. This Sp-binding GC-rich region of the TNIP1 promoter also participates in transcriptional activation by ligand-bound RAR. Together, these results demonstrate newly identified regulators of TNIP1 expression and suggest possible transcription factor targets which in turn control TNIP1-related biological end points ranging from apoptosis to inflammatory diseases.
authors: Graduate Program in Pharmacology and Toxicology, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-3092, USA.
authors: Priscilla C
authors: PC
authors: Encarnacao
authors: Vincent P
authors: VP
authors: Ramirez
authors: Carmen
authors: C
authors: Zhang
authors: Brian J
authors: BJ
authors: Aneskievich
mesh_terms: D001483:Base Sequence; D018938:Caco-2 Cells; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D019169:Jurkat Cells; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051705:Sp3 Transcription Factor / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; C117046:TNIP1 protein, human; D051705:Sp3 Transcription Factor