Abstract
Hes7, a bHLH gene essential for somitogenesis, displays cyclic expression of mRNA in the presomitic mesoderm (PSM). Here, we show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lunatic fringe (Lfng) transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors
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Biological Clocks / physiology*
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Cells, Cultured
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Cysteine Endopeptidases / metabolism
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Feedback, Physiological
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Expression Regulation, Developmental*
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Glycosyltransferases / genetics*
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Glycosyltransferases / metabolism
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Helix-Loop-Helix Motifs
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Mice
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Multienzyme Complexes / antagonists & inhibitors
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Multienzyme Complexes / metabolism
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Periodicity
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Promoter Regions, Genetic
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Protease Inhibitors / pharmacology
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Proteasome Endopeptidase Complex
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Somites / physiology*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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Ubiquitin / metabolism
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Up-Regulation
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Hes7 protein, mouse
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Multienzyme Complexes
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Protease Inhibitors
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Repressor Proteins
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Transcription Factors
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Ubiquitin
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Glycosyltransferases
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Lfng protein, mouse
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex