Sp sites contribute to basal and inducible expression of the human TNF{alpha}-Inducible Protein 3-Interacting Protein 1 (TNIP1) promoter

TNFα-induced protein 3-interacting protein 1 (TNIP1) is a corepressor of RAR and PPAR. Additionally, it can reduce signaling stemming from cell membrane receptors such as those for TNFα and EGF. 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 impact multiple important biological endpoints. 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 specificity protein (Sp) sites, responsive to both Sp1 and Sp3. EMSA and ChIP demonstrated physical binding between Sp1, Sp3 at these sites. Decrease of Sp1 protein levels via siRNA 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 endpoints ranging from apoptosis to inflammatory diseases.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Gene Source Type: research