Epigenetic Regulation of the Molecular Clockwork - Progress in Molecular Biology and Translational Science - page 37

JARID1A appears to regulate rhythmic gene transcription in part via its abil-
ity to inhibit histone deacetylation. 19 Finally, the EZH2 protein also affects
histone methylation in a rhythmic manner, acting predominately at H3K27
to alter gene transcription at relevant promoter sites. 23,45 Other jumonji
domain-containing proteins are also implicated in circadian transcription.
Specifically, Jmj5B ( Kdm8 ) is oscillatory in expression and contributes to
circadian timekeeping. 46 Loss of this protein in both mammalian systems
and Arabidopsis causes a phase advance in the circadian cycle.
Finally, a number of other enzymes involved in histone tail methylation
have also been observed to be important in the maintenance of the clock in
cells. The lysine methyltransferase SET1 in Neurospora plays an interesting
role in frq expression and changing not only trimethylation at H3K4 but
via this modification, allowing methylation of the DNA itself. 47
2. CIRCADIAN EPIGENETICS AND SYNAPTIC PLASTICITY
IN THE BRAIN
The role of transcription in synaptic plasticity has long been known
but only recently has the role of chromatin modification in driving synaptic
plasticity been appreciated. 6 The role of histone modifications in chromatin
structure appears to be as important in neuronal communication as it is for
cells of the periphery to perform their functions. The role of chromatin
structure in driving synaptic plasticity is an essential component of circadian
physiology as the brain houses the “master” circadian clock for the body. 48
Specifically, in mammals, the suprachiasmatic nucleus (composed of two
small lobes in the anterior hypothalamus) drives many circadian rhythms
in the body and lesion of this region causes arrhythmicity of an organism. 49
As an essential driver of circadian rhythmicity, the role of gene transcription
in this region is essential for normal clock ticking across the body. The dis-
covery of epigenetic processes at work in the SCN as well as in other regions
within the central nervous system has underscored the importance of chro-
matin structure in driving additional physiological processes.
2.1. Light and epigenetics in the suprachiasmatic nucleus
The mammalian SCN responds to light via neurons extending from the ret-
ina via the retinohypothalamic tract, providing synchronization to the sur-
rounding light/dark cycles. The circadian clock must undergo
reentrainment in order for an organism to synchronize with its environment.
This process is extremely important due to the fact that humans are often