Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock.
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.
Bessho
Yasumasa
Y
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan. ybessho@virus.kyoto-u.ac.jp
Hirata
Hiromi
H
Masamizu
Yoshito
Y
Kageyama
Ryoichiro
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000502:physiology*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism; D025461:Feedback, Physiological; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D010507:Periodicity; D011401:Promoter Regions, Genetic; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019170:Somites / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D015854:Up-Regulation
D051792:Basic Helix-Loop-Helix Proteins; D003546:Cysteine Endopeptidases; D016695:Glycosyltransferases; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D046988:Proteasome Endopeptidase Complex; D012097:Repressor Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C430525:Hes7 protein, mouse; C498392:Lfng protein, mouse