BACKGROUND: It is now becoming clear that the circadian rhythm of behaviours and hormones arises from a rhythm at the level of gene expression, and that mammals and Drosophila essentially use homologous genes as molecular gears in the control of circadian oscillation. In Drosophila, the period and timeless genes form a functional unit of the clock and its autoregulatory feedback loop for circadian rhythm. However, in mammals, the counterpart of timeless has not been found. RESULTS: We have isolated a mammalian homologue of timeless, mTim, from the mouse brain. mTim is highly expressed, with a weak or absent rhythm in the suprachiasmatic nucleus, the mammalian circadian centre. In the retina, mTim mRNA was found to be expressed with a circadian rhythm, and a particularly robust cycle was observed in the presence of light/dark cycles. We demonstrated that mTIM physically associates with mPER1 in vitro and in the nuclei of cultured COS7 cells. CONCLUSIONS: We have reported the isolation of the mouse timeless cDNA, the expression of the mTim mRNA and an interaction of mTIM with mPER1. These results indicate that the autoregulatory feedback mechanism of circadian oscillation of the period gene may also be conserved in mammals.
BACKGROUND: It is now becoming clear that the circadian rhythm of behaviours and hormones arises from a rhythm at the level of gene expression, and that mammals and Drosophila essentially use homologous genes as molecular gears in the control of circadian oscillation. In Drosophila, the period and timeless genes form a functional unit of the clock and its autoregulatory feedback loop for circadian rhythm. However, in mammals, the counterpart of timeless has not been found. RESULTS: We have isolated a mammalian homologue of timeless, mTim, from the mouse brain. mTim is highly expressed, with a weak or absent rhythm in the suprachiasmatic nucleus, the mammalian circadian centre. In the retina, mTim mRNA was found to be expressed with a circadian rhythm, and a particularly robust cycle was observed in the presence of light/dark cycles. We demonstrated that mTIM physically associates with mPER1 in vitro and in the nuclei of cultured COS7 cells. CONCLUSIONS: We have reported the isolation of the mousetimeless cDNA, the expression of the mTim mRNA and an interaction of mTIM with mPER1. These results indicate that the autoregulatory feedback mechanism of circadian oscillation of the period gene may also be conserved in mammals.
Authors: K Yagita; S Yamaguchi; F Tamanini; G T van Der Horst; J H Hoeijmakers; A Yasui; J J Loros; J C Dunlap; H Okamura Journal: Genes Dev Date: 2000-06-01 Impact factor: 11.361
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Authors: Elad B Rubin; Yair Shemesh; Mira Cohen; Sharona Elgavish; Hugh M Robertson; Guy Bloch Journal: Genome Res Date: 2006-10-25 Impact factor: 9.043
Authors: P L Lowrey; K Shimomura; M P Antoch; S Yamazaki; P D Zemenides; M R Ralph; M Menaker; J S Takahashi Journal: Science Date: 2000-04-21 Impact factor: 47.728
Authors: Erik Engelen; Roel C Janssens; Kazuhiro Yagita; Veronique A J Smits; Gijsbertus T J van der Horst; Filippo Tamanini Journal: PLoS One Date: 2013-02-13 Impact factor: 3.240