By Ethan D. Buhr, Joseph S. Takahashi (auth.), Achim Kramer, Martha Merrow (eds.)
This e-book presents the reader with a modern and accomplished evaluation concerning the molecular, mobile and system-wide ideas of circadian clock law. Emphasis is put on the significance of circadian clocks for the timing of healing interventions.
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Extra resources for Circadian Clocks
Furthermore, renal sodium reabsorption is compromised and arterial blood pressure is reduced in the ClockÀ/À mice (Zuber et al. 2009). Loss of BMAL1, which renders mice completely arrhythmic (Bunger et al. 2000), also leads to disruption of oscillations in glucose and triglyceride levels (Rudic et al. 2004). To address the question of whether the metabolic defects are due to a loss of rhythmicity in the SCN or in the peripheral clocks, mice with tissue-specific deletion of Bmal1 in the liver or pancreas have been generated.
2002). ” It is defined as the study of heritable changes in gene expression that does not involve any change to the DNA sequence. Such changes in gene expression can be brought about by a variety of mechanism that involves a combination of posttranslational modifications of histones, remodeling of chromatin, incorporation of histone variants, or methylation of DNA on CpG islands. Histone acetylation is a mark for activation of transcription, which is achieved by remodeling the chromatin to make it more accessible to the transcription machinery (Jenuwein and Allis 2001).
1). Importantly, circadian gene expression and BMAL1 acetylation are compromised in liver-specific SIRT1 mutant mice (Nakahata et al. 2008). While BMAL1 acetylation acts as a signal for CRY recruitment (Hirayama et al. 2007), PER2 acetylation enhances its stability (Asher et al. 2008). These findings led to the concept that SIRT1 operates as a rheostat of the circadian machinery, modulating the amplitude and “tightness” of CLOCK-mediated acetylation and consequent transcription cycles in metabolic tissues (Nakahata et al.