Epigenetic Regulation of the Molecular Clockwork - Progress in Molecular Biology and Translational Science - page 39

Light uses the signal transduction pathways described above to induce phos-
phorylation of H3 and subsequently drive induction of the c-Fos and Per1
genes. This observation led to the idea that chromatin modification at cir-
cadianly expressed genes might be important for driving their rhythmic
expression. Subsequently, numerous studies now reveal that changes in his-
tone protein posttranslational modifications are a driving force in the circa-
dian expression of CCGs. 22,26,30,57 This is true of mammalian and
nonmammalian systems. For example, dynamic chromatin modifications
occur in the Arabidopsis CCA1/LHY and TOC1 regulatory regions and
are an essential part of circadian rhythms in this organism. 58
It is interesting to speculate whether histone acetylation at promoters of
genes necessary for long-term memory is rhythmic. There is accumulating
evidence that synaptic plasticity, the basis of all cognitive processes, involves
the circadian clock. 59 The basic MAPK pathway, which is necessary for both
circadian rhythms in the SCN and for long-term memory formation in the
hippocampus, is under circadian control and involves rhythmicity in CREB
activation and subsequent gene transcription. 60 Interestingly, histone acet-
ylation at promoters of genes in the central nervous is an important process
which is required for long-term memory formation. 61 To date, little has
been done to address whether this activity is a rhythmic event in regions
of the central nervous system associated with learning and memory; but
based on the circadian oscillation of upstream events, it is quite likely to
be so. What is known is that both acetylation and methylation occur in
the central nervous system and both types of modifications have been dem-
onstrated to produce effects on cognition. After a learning event, the tran-
scription factor CREB is activated by phosphorylation, allowing its binding
to CREs. 62 This event is an essential step for the formation of long-term
memory. Interestingly, HDAC inhibitors have been shown to enhance syn-
aptic plasticity and memory, a process that is in part mediated by the HAT
activity of CREB and CBP. 63 Among other tasks dependent on CREB-
mediated gene transcription, the object recognition task (a hippocampus-
dependent learning paradigm) has been demonstrated to be influenced by
HDAC inhibitors in a CBP-dependent manner. 64

3. LINKING THE CIRCADIAN METABOLOME AND
METABOLISM TO EPIGENETICS
While genetics

are essential for the maintenance of energy

balance, 65-67

numerous studies have revealed that environmental cues