Clock genes

Antoch M, Kondratov R, Takahashi J (2005) Circadian clock genes as modulators of sensitivity to genotoxic stress. Cell Cycle 4901-907... 

Clock gene and transcription factor with histone acetyl-transferase (HAT) activity that (in complex with BMAL1) constitutes a positive limb of molecular circadian oscillators. 

Period 1) Clock gene and transcriptional repressor and negative limb (complex with CRY, PER2) of molecular circadian oscillators, essential for circadian clock plasticity and entrainment. 

At its most fundamental level, the circadian cycle rests on the influence of so-called clock genes . These genes have been studied most extensively in insects but they have also been found in humans. Their protein products enter the cell nucleus and regulate their own transcription. This feedback process is linked to exposure to light and so it is not surprising that visual inputs are important for maintenance of circadian rhythms. However, it is not the reception of specific visual information, transmitted in the optic nerve to the lateral geniculate nucleus (LGN) and visual cortex (i.e. visual discrimination), that is responsible for the rhythm but the more simple, almost subconscious, reception of light. 

McClung C., Sidiropoulou K, Vitaterna M. et al (2005). Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc. Natl. Acad. Sci. USA 102, 9377-81. 

Phase-shifting by melatonin is attributed to its action at MT2 receptors present in the SCN (Liu et al. 1997). The chronobiological effect of melatonin is due to its direct influence on the electrical and metabolic activity of the SCN, a finding that has been confirmed both in vivo and in vitro. The application of melatonin directly to the SCN significantly increases the amplitude of the melatonin peak, thereby suggesting that in addition to its phase-shifting effect melatonin directly acts on the amplitude of the oscillations (Pevet et al. 2002). However, this amplitude modulation seems to be unrelated to clock gene expression in the SCN (Poirel et al. 2003). 

Poirel, V. J., Boggio, V., Dardente, H. et al. (2003). Contrary to other non-photic cues, acute melatonin injection does not induce immediate changes of clock gene mrna expression in the rat suprachiasmatic nuclei. Neuroscience 120, 745-55. 

Caldelas, I., Tejadilla D., Gonzalez B., Montufar R. and Hudson R. (2007) Diurnal pattern of clock gene expression in the hypothalamus of the newborn rabbit. Neurosci. 144, 395—401. 

Van Gelder We are currently making the JLdjBmal mice to answer that question. Rae Silver has some results relating to this. She has looked for clock gene expression in the melanopsin-positive ganglion cells. Remarkably, she does not find Per expression in those cells. 

In mammalian tissue culture cells, robust circadian gene expression can be entrained by 12 h temperature cycles with an amplitude of 4 °C (e.g. 37 °C versus 33 °C) (Brown et al 2002). We thus wondered whether physiological temperature rhythms, themselves circadian and with an amplitude of —4 °C in most mammals, could also sustain cyclic clock-gene transcription. To this end, we engineered a... 

Terazono H, Mutoh T, Yamaguchi S et al 2003 Adrenergic regulation of clock gene expression in mouse liver. Proc Natl Acad Sci USA 100 6795-6800 Tosini G, Menaker M 1996 Circadian rhythms in cultured mammalian retina. Science 272 419-421... 

What is special about the testis that requires the absence of the circadian clock so pervasive in other tissues The testis has a number of characteristics, which make it quite different from other tissues. The testis contains spermatogenic cells that perform a constant and complex cell differentiation program where reductive cell divisions occur. It may be that the complex pattern of gene expression engendered by the circadian clock leads to unfavourable interactions with the developmental process of paramount importance to the testis. Alternatively, the normal oscillation of clock gene expression may be distorted by other transcriptional regulators or co-activators which are only present in seminiferous tubules (Sassone-Corsi 2002). 

Cermakian N, Monaco L, Pando MP, Dierich A, Sassone-Corsi P 2001 Altered behavioral rhythms and clock gene expression in mice with a targeted mutation in the Periodl gene. EMBO J 20 3967-3974... 

Cermakian N, Pando MP, Thompson CL et al 2002 Light induction of a vertebrate clock gene involves signaling through blue-light receptors and MAP kinases. Curr Biol 12 844—848... 

Okamura We didn t measure the clock gene expression in peripheral tissues. But there are indications that some signals were transmitted from the SCN transplant to the cortex. 

Schibler As I remember from Woody Hastings work in Gonjaulax, where the clock genes are not known, everything seems to be regulated on the level of translation and protein stabihty. 

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