Dec1 and Dec2 are regulators of the mammalian molecular clock

Nature. 2002 Oct 24;419(6909):841-4. doi: 10.1038/nature01123.

Abstract

The circadian rhythms in mammals are regulated by a pacemaker located in the suprachiasmatic nucleus of the hypothalamus. Four clock-gene families have been found to be involved in a transcription-translation feedback loop that generates the circadian rhythm at the intracellular level. The proteins Clock and Bmal1 form a heterodimer which activates the transcription of the Per gene from the E-box elements in its promoter region. Protein products of Per act together with Cry proteins to inhibit Per transcription, thus closing the autoregulatory feedback loop. We found that Dec1 and Dec2, basic helix-loop-helix transcription factors, repressed Clock/Bmal1-induced transactivation of the mouse Per1 promoter through direct protein-protein interactions with Bmal1 and/or competition for E-box elements. Dec1 and Dec2 are expressed in the suprachiasmic nucleus in a circadian fashion, with a peak in the subjective day. A brief light pulse induced Dec1 but not Dec2 expression in the suprachiasmic nucleus in a phase-dependent manner. Dec1 and Dec2 are regulators of the mammalian molecular clock, and form a fifth clock-gene family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks / genetics*
  • CLOCK Proteins
  • Cell Cycle Proteins
  • Circadian Rhythm / genetics*
  • DNA / genetics
  • DNA / metabolism
  • Electrophoretic Mobility Shift Assay
  • Feedback, Physiological
  • Gene Expression Regulation*
  • Genes, Reporter / genetics
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • In Situ Hybridization
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Period Circadian Proteins
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Response Elements / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Arntl protein, mouse
  • BHLHE40 protein, human
  • BHLHE41 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Bhlhb3 protein, mouse
  • Bhlhe40 protein, mouse
  • Bhlhe40 protein, rat
  • Bhlhe41 protein, rat
  • Cell Cycle Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • PER1 protein, human
  • Per1 protein, mouse
  • Per1 protein, rat
  • Period Circadian Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • DNA
  • CLOCK Proteins
  • CLOCK protein, human
  • Clock protein, mouse
  • Clock protein, rat

Associated data

  • GENBANK/AB012601
  • GENBANK/AB014558
  • GENBANK/AB016532
  • GENBANK/AF000998
  • GENBANK/AL040215
  • GENBANK/D84657