2. Academic Validation
  3. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription

Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription

  • Neuron. 1998 Nov;21(5):1101-13. doi: 10.1016/s0896-6273(00)80627-3.
A M Sangoram 1,  L Saez,  M P Antoch,  N Gekakis,  D Staknis,  A Whiteley,  E M Fruechte,  M H Vitaterna,  K Shimomura,  D P King,  M W Young,  C J Weitz,  J S Takahashi
Affiliations

Affiliation

  • 1 Department of Neurobiology and Physiology and National Science Foundation, Center for Biological Timing, The Rockefeller University, New York, New York 10021, USA.
PMID: 9856465 DOI: 10.1016/s0896-6273(00)80627-3
Abstract

We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.

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