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

 Young Mi Park  ;  Yong-ho Lee  ;  Soo Hyun Kim  ;  Eun Young Lee  ;  Kyung-Sup Kim  ;  Darren R. Williams  ;  Hyun Chul Lee 
 METABOLISM-CLINICAL AND EXPERIMENTAL, Vol.61(11) : 1622-1632, 2012 
Journal Title
Issue Date
3T3-L1 Cells ; Adiponectin/genetics* ; Animals ; Base Sequence ; Binding Sites ; Blotting, Western ; Chromatin Immunoprecipitation ; DNA Primers ; Electrophoretic Mobility Shift Assay ; Gene Silencing ; Humans ; Mice ; Polymerase Chain Reaction ; Promoter Regions, Genetic* ; Snail Family Transcription Factors ; Transcription Factors/genetics ; Transcription Factors/physiology*
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 -152 bp), 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Orofacial Pain and Oral Medicine (구강내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Yong Ho(이용호) ORCID logo https://orcid.org/0000-0002-6219-4942
Lee, Hyun Chul(이현철)
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