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

Ashvin M. Sangoram, Lino Saez, Marina P. Antoch, Nicholas Gekakis, David Staknis, Andrew Whiteley, Ethan M. Fruechte, Martha Hotz Vitaterna, Kazuhiro Shimomura, David P. King, Michael W. Young, Charles J. Weitz, Joseph S. Takahashi

Research output: Contribution to journalArticle

273 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1101-1113
Number of pages13
JournalNeuron
Volume21
Issue number5
DOIs
StatePublished - Nov 1998

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Drosophila
Drosophila Proteins
Suprachiasmatic Nucleus
Transcriptional Activation
Genes
Retina
Organism Cloning
Mammals
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mammalian circadian autoregulatory loop : A timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. / Sangoram, Ashvin M.; Saez, Lino; Antoch, Marina P.; Gekakis, Nicholas; Staknis, David; Whiteley, Andrew; Fruechte, Ethan M.; Vitaterna, Martha Hotz; Shimomura, Kazuhiro; King, David P.; Young, Michael W.; Weitz, Charles J.; Takahashi, Joseph S.

In: Neuron, Vol. 21, No. 5, 11.1998, p. 1101-1113.

Research output: Contribution to journalArticle

Sangoram, AM, Saez, L, Antoch, MP, Gekakis, N, Staknis, D, Whiteley, A, Fruechte, EM, Vitaterna, MH, Shimomura, K, King, DP, Young, MW, Weitz, CJ & Takahashi, JS 1998, 'Mammalian circadian autoregulatory loop: A timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription', Neuron, vol. 21, no. 5, pp. 1101-1113. https://doi.org/10.1016/S0896-6273(00)80627-3
Sangoram, Ashvin M. ; Saez, Lino ; Antoch, Marina P. ; Gekakis, Nicholas ; Staknis, David ; Whiteley, Andrew ; Fruechte, Ethan M. ; Vitaterna, Martha Hotz ; Shimomura, Kazuhiro ; King, David P. ; Young, Michael W. ; Weitz, Charles J. ; Takahashi, Joseph S. / Mammalian circadian autoregulatory loop : A timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. In: Neuron. 1998 ; Vol. 21, No. 5. pp. 1101-1113.
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