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changes in distinct physiological states promises to be important for our
future understanding of how the energy state of the cell couples epigenetics
to the circadian clock.
4. CONCLUSIONS
The elaborate mechanisms underlying the role of the circadian clock
in epigenetics are providing a whole new arena in which to study circadian
gene expression. The advancement of technology has assisted in this
endeavor. Specifically, high-throughput techniques have allowed the circa-
dian epigenome to be better elucidated across species and in a variety of
experimental conditions which have been enlightening for the field.
ChIP-seq and RNA-seq among other techniques have revealed the global
state of specific chromatin marks and binding proteins at specific chromo-
somal locations throughout the circadian cycle. In addition, an understand-
ing of the dynamic nature of the circadian metabolome has built on our
knowledge of the mechanisms underlying changes in chromatin structure
and function. Becoming increasingly evident is that the metabolic state of
the cell has a profound influence on circadian gene transcription not only
through the modification of transcription factors themselves but also via
the role they have in the activation of chromatin-modifying enzymes. In
addition, cellular metabolites play a central role in chromatin modification
by themselves serving as substrates or upstream intermediates that ultimately
drive chromatin marks in a rhythmic fashion. Considering this, it is impor-
tant to remember that energy intake is a rhythmic activity for most organ-
isms, and thus, it drives the circadian changes in overall cellular energy levels.
Recent studies showing that abnormal temporal energy intake can dramat-
ically influence metabolic homeostasis ultimately underscore the importance
of cellular metabolism and metabolites in driving rhythmic gene transcrip-
tion for metabolic health.
REFERENCES
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