Snail, a transcriptional regulator, represses adiponectin expression by directly binding to an E-box motif in the promoter.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Metabolism: clinical and experimental (Impact Factor: 3.61). 05/2012; 61(11):1622-32. DOI: 10.1016/j.metabol.2012.04.014
Source: PubMed

ABSTRACT 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.
To further understand how adiponectin expression is regulated, we isolated the human adiponectin promoter and analyzed its activity after serial deletions.
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.
Snail is a novel regulator of adiponectin expression and probably has a role in regulating adipogenesis.

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