Coupling circadian rhythms of metabolism and chromatin remodelling

Abstract

The circadian clock controls a large variety of neuronal, endocrine, behavioral and physiological responses in mammals. This control is exerted in large part at the transcriptional level on genes expressed in a cyclic manner. A highly specialized transcriptional machinery based on clock regulatory factors organized in feedback autoregulatory loops governs a significant portion of the genome. These oscillations in gene expression are paralleled by critical events of chromatin remodeling that appear to provide plasticity to circadian regulation. Specifically, the NAD+-dependent deacetylases SIRT1 and SIRT6 have been linked to circadian control of gene expression. This, and additional accumulating evidence, shows that the circadian epigenome appears to share intimate links with cellular metabolic processes and has remarkable plasticity showing reprogramming in response to nutritional challenges. In addition to SIRT1 and SIRT6, a number of chromatin remodelers have been implicated in clock control, including the histone H3K4 tri-methyltransferase MLL1. Deciphering the molecular mechanisms that link metabolism, epigenetic control and circadian responses will provide valauble insights towards innovative strategies of therapeutic intervention.

Hibernation impacts lysine methylation dynamics in the 13‐lined ground squirrel, Ictidomys tridecemlineatus

“…This is supported by significant changes over the torpor‐arousal cycle and tissue‐specific responses in (a) KMT protein levels, (b) KMT activities, and (c) lysine methylation levels of well‐known protein targets (histone H3, p53) of KMT action. Differential expression of KMT enzymes has already been shown to influence cellular activity in a manner that is dependent on interacting factors and the environmental context in nonhibernator systems (Masri, Orozco‐Solis, Aguilar‐Arnal, Cervantes, & Sassone‐Corsi, ; Son et al, ). Regulation via posttranslational modifications allows for rapid initiation and reversal of metabolic responses as well as coordinated control over diverse metabolic functions in cells.…”

The roles of gut microbiota and circadian rhythm in the cardiovascular protective effects of polyphenols

“…SIRT1 also deacetylates BMAL1 to affect its circadian regulatory activity (Belden & Dunlap, 2008). The SIRT1/PGC-1α axis is involved in the crosstalk between the circadian clock and energy metabolism (Masri, Orozco-Solis, Aguilar-Arnal, Cervantes, & Sassone-Corsi, 2015). PGC-1α, a target of SIRT1, is a strong transcription factor and the key regulator of energy metabolism and intimately involved in obesity and obesity-related cardiovascular disorders (Liang & Ward, 2006).…”

Phosphorylated SIRT1 associates with replication origins to prevent excess replication initiation and preserve genomic stability

“…SIRT1 affects chromatin modifications, DNA damage/repair, aging, circadian rhythms, and metabolism (25,26). SIRT1 has been explored as a potential molecular target for the treatment of cancer (27,28).…”