Clock genes : epigenetic modulation by stress

The functional unit of the internal circadian oscillator is found at the molecular level Many of these genes show circadian rhythms in their mRNA and/or protein expression, generated by self-sustained transcriptiontranslation feedback loops. The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN), the core clock machinery has been identified in almost all peripheral tissues, including the liver Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently. Feeding time is considered a dominant entrainment cue for peripheral and circadian gene expression in the liver,, kidney, heart, and pancreas. It does not influence the phase of clock gene expression in the SCN Mutations in the core-clock regulator, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), affect the transcriptional regulation of ROS-responsive genes, ROS homeostasis, and tolerance to oxidative stress.. In trun , ROS functions as an input signal that affects the transcriptional output of the clock, Also glucocorticoids, entrain the circadian rhythm by phase-shifting the expressions of several core clock genes in peripheral organs, including the liver, kidneys, and heart. Chronic stress affects the circadian rhythm of core clock gene expressions in the liver via the HPA axis Effects of absence of nursing mothers on the circadian pacemaker of their offspring alter clock genes, in rat Per1 (rPer1) and rPer2 expression rhythms in the pup suprachiasmatic nuclei (SCN) Long-term shiftwork resulted in the same promoter hypomethylation of CLOCK and hypermethylation of CRY2, as was previously observed in breast cancer case-control studies. We will discuss these results in the new chronobiological persective.