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Snail, a transcriptional regulator, represses adiponectin expression by directly binding to an E-box motif in the promoter.
- Source :
- Metabolism: Clinical & Experimental; Nov2012, Vol. 61 Issue 11, p1622-1632, 11p
- Publication Year :
- 2012
-
Abstract
- Abstract: Objective: Adiponectin is a hormone that modulates many metabolic processes and is exclusively expressed in adipose tissue. However, complete understanding of the factors that regulate adiponectin expression is lacking. The following were investigated: (1) functional analysis of the human adiponectin promoter, (2) putative adiponectin repressor sequence activity in 3T3-L1 adipocytes using promoter mutagenesis, (3) whether Snail, an E-box binding transcription factor, binds this repressor sequence, (4) if Snail regulates adiponectin expression in 3T3-L1 pre-adipocytes. Materials/Methods: To further understand how adiponectin expression is regulated, we isolated the human adiponectin promoter and analyzed its activity after serial deletions. Results: We found a negative cis-regulatory element located in the adiponectin proximal promoter sequence (−174 to −152bp), which contained an E-box site (CAACTG). The DNA binding activity of this putative negative regulatory factor was found to be sequence-specific and the binding activity is decreased during adipocyte differentiation time-dependently. Affinity chromatography identified the zinc-finger transcription factor Snail (SNAI1) as the putative negative regulatory factor. Chromatin immunoprecipitation assay and electrophoretic mobility shift assay confirmed that Snail binds to this negative cis-regulatory element in pre-adipocytes, exclusively. Inhibition of Snail expression using small interfering RNA techniques increased adiponectin expression in 3T3-L1 adipocytes, while overexpression of Snail reduced adiponectin expression. Furthermore, we observed an inverse relation between the expression of Snail and the expression of CCAAT-enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma, which are transcription factors that regulate adipogenesis. Conclusions: Snail is a novel regulator of adiponectin expression and probably has a role in regulating adipogenesis. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 00260495
- Volume :
- 61
- Issue :
- 11
- Database :
- Supplemental Index
- Journal :
- Metabolism: Clinical & Experimental
- Publication Type :
- Academic Journal
- Accession number :
- 82612426
- Full Text :
- https://doi.org/10.1016/j.metabol.2012.04.014