Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop

Science. 2002 Oct 25;298(5594):840-3. doi: 10.1126/science.1074560.

Abstract

Transcription of messenger RNAs (mRNAs) for Notch signaling molecules oscillates with 2-hour cycles, and this oscillation is important for coordinated somite segmentation. However, the molecular mechanism of such oscillation remains to be determined. Here, we show that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity. Cycling is cell-autonomous and depends on negative autoregulation of hes1 transcription and ubiquitin-proteasome-mediated degradation of Hes1 protein. Because Hes1 oscillation can be seen in many cell types, this clock may regulate timing in many biological systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks
  • Blood
  • Cell Line
  • Cycloheximide / pharmacology
  • Cysteine Endopeptidases / metabolism
  • Feedback, Physiological
  • Gene Expression Regulation
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism
  • Half-Life
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Leupeptins / pharmacology
  • Mesoderm / metabolism
  • Mice
  • Multienzyme Complexes / metabolism
  • PC12 Cells
  • Periodicity*
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex
  • Protein Biosynthesis
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Transcription Factor HES-1
  • Transcription, Genetic
  • Transfection
  • Ubiquitin / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hes1 protein, mouse
  • Hes1 protein, rat
  • Homeodomain Proteins
  • Leupeptins
  • Multienzyme Complexes
  • Protease Inhibitors
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Transcription Factor HES-1
  • Ubiquitin
  • lactacystin
  • Cycloheximide
  • Glycosyltransferases
  • Lfng protein, mouse
  • Lfng protein, rat
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • Acetylcysteine