Abstract
Snail, a zinc-finger transcriptional repressor, is essential for mesoderm and neural crest cell formation and epithelial-mesenchymal transition. The basic helix-loop-helix transcription factors E2A and Twist have been linked with Snail during embryonic development. In this study, we examined the role of Snail in cellular differentiation through regulation of p21(WAF/CIP1) expression. A reporter assay with the p21 promoter demonstrated that Snail inhibited expression of p21 induced by E2A. Co-expression of Snail with Twist showed additive inhibitory effects. Deletion mutants of the p21 promoter revealed that sequences between -270 and -264, which formed a complex with unidentified nuclear factor(s), were critical for E2A and Snail function. The E2A-dependent expression of the endogenous p21 gene was also inhibited by Snail.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle Proteins / metabolism*
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Cell Differentiation / genetics
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Cell Line
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Expression Regulation / physiology
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Humans
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Nuclear Proteins / metabolism*
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Osteoblasts / cytology*
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Osteoblasts / metabolism*
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Recombinant Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Snail Family Transcription Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Twist-Related Protein 1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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DNA-Binding Proteins
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Nuclear Proteins
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Recombinant Proteins
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Repressor Proteins
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Snail Family Transcription Factors
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TCF3 protein, human
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TWIST1 protein, human
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Transcription Factors
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Twist-Related Protein 1