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Left-right axis asymmetry determining human Cryptic gene is transcriptionally repressed by Snail
Published in BioMed Central Ltd.
2016
PMID: 27793090
Volume: 16
   
Issue: 1
Pages: 1 - 10
Abstract
Background: Establishment of the left-right axis is important for positioning organs asymmetrically in the developing vertebrate-embryo. A number of factors like maternally deposited molecules have emerged essential in initiating the specification of the axis; the downstream events, however, are regulated by signal-transduction and gene-expression changes identifying which remains a crucial challenge. The EGF-CFC family member Cryptic, that functions as a co-receptor for some TGF-beta ligands, is developmentally expressed in higher mammals and mutations in the gene cause loss or change in left-right axis asymmetry. Despite the strong phenotype, no transcriptional-regulator of this gene is known till date. Results: Using promoter-analyses tools, we found strong evidence that the developmentally essential transcription factor Snail binds to the human Cryptic-promoter. We cloned the promoter-region of human Cryptic in a reporter gene and observed decreased Cryptic-promoter activation upon increasing Snail expression. Further, the expression of Cryptic is down-regulated upon exogenous Snail expression, validating the reporter assays and the previously identified role of Snail as a transcriptional repressor. Finally, we demonstrate using gel-shift assay that Snail in nuclear extract of PANC1 cells interacts with the promoter-construct bearing putative Snail binding sites and confirm this finding using chromatin immunoprecipitation assay. Conclusions: Snail represses the expression of human Cryptic and therefore, might affect the signaling via Nodal that has previously been demonstrated to specify the left-right axis using the EGF-CFC co-receptors. © 2016 The Author(s).
About the journal
JournalBMC Developmental Biology
PublisherBioMed Central Ltd.
ISSN1471213X
Open AccessYes
Concepts (29)
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    CFC1 PROTEIN, HUMAN
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    Signal peptide
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    SNAI1 PROTEIN, HUMAN
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    TRANSCRIPTION FACTOR SNAIL
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    Binding site
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    Cell line
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    EMBRYO DEVELOPMENT
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    Gene expression regulation
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    Genetic transcription
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    Genetics
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    Hek293 cell line
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    Human
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    Metabolism
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    Molecular cloning
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    MORPHOGENESIS
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    Promoter region
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    REPORTER GENE
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    Binding sites
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    BODY PATTERNING
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    Cloning, molecular
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    EMBRYONIC DEVELOPMENT
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    Gene expression regulation, developmental
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    GENES, REPORTER
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    Hek293 cells
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    Humans
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    Intercellular signaling peptides and proteins
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    Promoter regions, genetic
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    SNAIL FAMILY TRANSCRIPTION FACTORS
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    Transcription, genetic