Abstract
The left-right (L-R) asymmetric expression of lefty2 and nodal is controlled by a left side-specific enhancer (ASE). The transcription factor FAST2, which can mediate signaling by TGF beta and activin, has now been identified as a protein that binds to a conserved sequence in ASE. These FAST2 binding sites were both essential and sufficient for L-R asymmetric gene expression. The Fast2 gene is bilaterally expressed when nodal and lefty2 are expressed on the left side. TGF beta and activin can activate the ASE activity in a FAST2-dependent manner, while Nodal can do so in the presence of an EGF-CFC protein. These results suggest that the asymmetric expression of lefty2 and nodal is induced by a left side-specific TGF beta-related factor, which is most likely Nodal itself.
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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Animals
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Base Sequence
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Cloning, Molecular
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Conserved Sequence
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Embryo, Mammalian
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Embryo, Nonmammalian
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Enhancer Elements, Genetic
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Feedback
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Forkhead Transcription Factors
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Gene Expression Regulation*
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Left-Right Determination Factors
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Mice
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Mice, Transgenic
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Nodal Protein
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Signal Transduction
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Transcription Factors / metabolism
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Transcription, Genetic*
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Transforming Growth Factor beta / genetics*
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Xenopus laevis
Substances
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DNA-Binding Proteins
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Forkhead Transcription Factors
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Foxh1 protein, mouse
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Left-Right Determination Factors
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Nodal Protein
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Nodal protein, mouse
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Recombinant Fusion Proteins
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Recombinant Proteins
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Transcription Factors
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Transforming Growth Factor beta