Snail1 transcriptional repressor binds to its own promoter and controls its expression.
The product of Snail1 gene is a transcriptional repressor of E-cadherin expression and an inductor of the epithelial-mesenchymal transition in several epithelial tumour cell lines. Transcription of Snail1 is induced when epithelial cells are forced to acquire a mesenchymal phenotype. In this work we demonstrate that Snail1 protein limits its own expression: Snail1 binds to an E-box present in its promoter (at -146 with respect to the transcription start) and represses its activity. Therefore, mutation of the E-box increases Snail1 transcription in epithelial and mesenchymal cells. Evidence of binding of ectopic or endogenous Snail1 to its own promoter was obtained by chromatin immunoprecipitation (ChIP) experiments. Studies performed expressing different forms of Snail1 under the control of its own promoter demonstrate that disruption of the regulatory loop increases the cellular levels of Snail protein. These results indicate that expression of Snail1 gene can be regulated by its product and evidence the existence of a fine-tuning feed-back mechanism of regulation of Snail1 transcription.
Peiró
Sandra
S
Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, c/ Doctor Aiguader, 80, 08003 Barcelona, Spain.
Escrivà
Maria
M
Puig
Isabel
I
Barberà
Maria José
MJ
Dave
Natàlia
N
Herranz
Nicolás
N
Larriba
Maria Jesús
MJ
Takkunen
Minna
M
Francí
Clara
C
Muñoz
Alberto
A
Virtanen
Ismo
I
Baulida
Josep
J
García de Herreros
Antonio
A
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D024721:E-Box Elements; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors