Circadian rhythms and memory formation: regulation by chromatin remodeling

Abstract

Epigenetic changes, such as DNA methylation or histone modification, can remodel the chromatin and regulate gene expression. Remodeling of chromatin provides an efficient mechanism of transducing signals, such as light or nutrient availability, to regulate gene expression. CLOCK:BMAL1 mediated activation of clock-controlled genes (CCGs) is coupled to circadian changes in histone modification at their promoters. Several chromatin modifiers, such as the deacetylases SIRT1 and HDAC3 or methyltransferase MLL1, have been shown to be recruited to the promoters of the CCGs in a circadian manner. Interestingly, the central element of the core clock machinery, the transcription factor CLOCK, also possesses histone acetyltransferase activity. Rhythmic expression of the CCGs is abolished in the absence of these chromatin modifiers. Recent research has demonstrated that chromatin remodeling is at the cross-roads of circadian rhythms and regulation of metabolism and aging. It would be of interest to identify if similar pathways exist in the epigenetic regulation of memory formation.

AMP-activated protein kinase as a key molecular link between metabolism and clockwork

“…14 D-box-binding protein binds to D-boxes (TTA (T/C) GTAA), whereas RORα and Rev-Erbα bind to the Rev-Erb/ROR binding element, or RRE [(A/T) A (A/T) NT (A/G) GGTCA]. Approximately 10% of the transcriptome displays robust circadian rhythmicity.…”

Modeling Biological Rhythms in Cell Populations

“…There is strong evidence that the progression through the cell cycle is gated by the circadian clock genes, resulting in daily waves of DNA synthesis and mitosis in many tissues. It has been proposed that circadian gating of the cell cycle might have evolved to protect dividing cells from harmful environment like UV, or to help coordinating metabolic activity [46]. Regardless of the implication at the molecular level, the growth rate of cell populations can vary significantly under clock control.…”

Metabolic Signaling to Chromatin

“…The involvement of SIRT1 in circadian regulation showed a direct link between cyclic rhythms and energy metabolism in the cell (Sahar and Sassone-Corsi 2012). Given that the expression levels of the SIRT1 gene and protein are noncyclic (Nakahata et al 2008), a major question has been: How can two regulators (CLOCK and SIRT1) that are mostly expressed in a nonoscillatory manner lead to the circadian regulated acetylation of histone H3K9/K14 and BMAL1K537?…”

“…A wide variety of physiological functions, including sleepwake cycles, body temperature, hormone secretion, locomotor activity, and feeding behavior depend on the circadian clock-a highly conserved system that enables organisms to adapt to common daily changes, such as the day-night cycle and food availability (Reppert and Weaver 2002;Sahar and Sassone-Corsi 2012). Based on evidence accumulated over several decades, circadian rhythms represent possibly the most prominent area of physiology that has effectively been studied using systems biology.…”