Epigenetic Regulation of the Molecular Clockwork - Progress in Molecular Biology and Translational Science - page 29

CHAPTER TWO

Epigenetic Regulation of the
Molecular Clockwork

Kristin Eckel-Mahan, Paolo Sassone-Corsi
Center for Epigenetics and Metabolism, University of California, Irvine, California, USA

Contents
1.

Introduction to Epigenetics and the Circadian Clock 30

1.1 Histone proteins under circadian control 32

1.2 Histone acetylases under circadian control 32

1.3 Histone deacetylases under circadian control 34

1.4 Other histone protein modifiers associated with the circadian clock 36

2. Circadian Epigenetics and Synaptic Plasticity in the Brain 37

2.1 Light and epigenetics in the suprachiasmatic nucleus 37

3. Linking the Circadian Metabolome and Metabolism to Epigenetics 39

3.1 The role of specific metabolites in chromatin structure 42

4. Conclusions 45

References 45

Abstract
Circadian rhythms control a wide range of physiological events in all organisms. Typical
of our modern lifestyles is the flexibility to rest, exercise, eat, or socialize at any time of
the circadian day or night; yet, these allowances correlate with rising disorders of a met-
abolic nature, which are thought to be mediated by changes in the molecular events
underlying metabolic gene expression. Because the clock confers on gene expression
changes in activity that are not necessarily related to changes in DNA sequence, the
study of circadian rhythms is inseparable from epigenetics. Increasingly evident is that
energy balance at the systems level relies on precise and collaborative circadian timing
of epigenetic events within individual cells and tissues of the body. At the center of
these rhythms resides the circadian clock machinery, a remarkably well-orchestrated
transcription - translation feedback system that incorporates a fluctuating landscape
of mRNA expression, protein stability, chromatin state, and metabolite abundance to
keep correct time. Understanding more fully the ties that exist between cellular metab-
olism and the circadian clock at the epigenetic level will produce not only needed
insights about circadian physiology but also novel strategies for the pharmacological
and nonpharmacological treatment of metabolic disorders.