Human TNFα-induced protein 3-interacting protein 1 (TNIP1) promoter activation is regulated by retinoic acid receptors

Coregulator proteins play key roles in transcriptional control by members of the nuclear receptor superfamily. Previously, we demonstrated that tumor necrosis factor α (TNFα)-induced protein 3-interacting protein 1 (TNIP1) is a corepressor of agonist-bound retinoic acid receptors (RARs). Additionall...

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Published in:	Gene Vol. 515; no. 1; pp. 42 - 48
Main Authors:	Gurevich, Igor, Zhang, Carmen, Francis, Nidhish, Struzynsky, Charles P., Livings, Sarah E., Aneskievich, Brian J.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-02-2013
Subjects:	Cell Line DNA-Binding Proteins - genetics epigenetics Feedback Gene Expression Regulation - drug effects Gene regulation Human immunodeficiency virus Humans luciferase Nef protein NF- Kappa B protein Nuclear receptor Nuclear receptors Peroxisome proliferator-activated receptors Promoter promoter regions Promoter Regions, Genetic - drug effects Promoters Protein Binding RAR receptors Receptors, Retinoic Acid - metabolism Regulatory sequences response elements Response Elements - drug effects retinoic acid Retinoic acid receptors TNIP1 transcription (genetics) transcription factor NF-kappa B Transcription factors Transcriptional Activation - drug effects Tretinoin - pharmacology Tumor necrosis factor- alpha TNFα RAR Nuclear receptor RIP140 TSA NR RARE DR2 DR5 ChIP RXR Promoter NF-κB HIV TNIP1 PPAR Sp1 EMSA qPCR ATRA HDAC
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Summary:	Coregulator proteins play key roles in transcriptional control by members of the nuclear receptor superfamily. Previously, we demonstrated that tumor necrosis factor α (TNFα)-induced protein 3-interacting protein 1 (TNIP1) is a corepressor of agonist-bound retinoic acid receptors (RARs). Additionally, TNIP1 has been shown to repress peroxisome proliferator-activated receptors (PPAR) and NF-κB activity and interact with HIV proteins nef and matrix. TNIP1 transcriptional regulation, however, is under studied. Here we show that under permissive epigenetic conditions, TNIP1 expression is induced by all trans retinoic acid (ATRA). Within a 6000bp region of the human TNIP1 promoter we cloned, both proximal and distal promoter regions are RAR responsive with the latter having RA response elements (RAREs) recognizable by their sequence and functionality in native promoter and synthetic RARE luciferase constructs, EMSA, and ChIP assays. These findings suggest a feedback loop whereby RARs activate expression of TNIP1, which then attenuates their activity. Together with anticipated constitutive transcription factors and the previously described NF-κB-responsiveness of the proximal TNIP1 promoter, the expected combinatorial control of TNIP1 expression could likely modulate TNIP1's impact in any of its target pathways. The degree of control by RARs or other transcription factors would in turn depend on their cell-specific level of expression and/or activation from signals in the environment such as ATRA and TNFα. ► Putative RAR binding sites were identified in 6kb promoter of human TNIP1 gene. ► The cloned TNIP1 promoter is ATRA and RAR responsive. ► The TNIP1 gene is ATRA inducible under permissive epigenetic conditions. ► Two distinct functional RAREs were confirmed in TNIP1 promoter. ► Control over TNIP1 expression depends on complex transcription factor interplay.
Bibliography:	http://dx.doi.org/10.1016/j.gene.2012.11.041 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0378-1119 1879-0038
DOI:	10.1016/j.gene.2012.11.041