Circadian rhythms in the three-dimensional genome: implications of chromatin interactions for cyclic transcription
Por:
Pacheco-Bernal I., Becerril-Pérez F., Aguilar-Arnal L.
Publicada:
15 may 2019
Resumen:
Circadian rhythms orchestrate crucial physiological functions and
behavioral aspects around a day in almost all living forms. The
circadian clock is a time tracking system that permits organisms to
predict and anticipate periodic environmental fluctuations. The
circadian system is hierarchically organized, and a master pacemaker
located in the brain synchronizes subsidiary clocks in the rest of the
organism. Adequate synchrony between central and peripheral clocks
ensures fitness and potentiates a healthy state. Conversely, disruption
of circadian rhythmicity is associated with metabolic diseases,
psychiatric disorders, or cancer, amongst other pathologies. Remarkably,
the molecular machinery directing circadian rhythms consists of an
intricate network of feedback loops in transcription and translation
which impose 24-hcycles in gene expression across all tissues.
Interestingly, the molecular clock collaborates with multitude of
epigenetic remodelers to fine tune transcriptional rhythms in a
tissue-specific manner. Very exciting research demonstrate that
three-dimensional properties of the genome have a regulatory role on
circadian transcriptional rhythmicity, from bacteria to mammals.
Unexpectedly, highly dynamic long-range chromatin interactions have been
revealed during the circadian cycle in mammalian cells, where thousands
of regulatory elements physically interact with promoter regions every
24 h. Molecular mechanisms directing circadian dynamics on chromatin
folding are emerging, and the coordinated action between the core clock
and epigenetic remodelers appears to be essential for these movements.
These evidences reveal a critical epigenetic regulatory layer for
circadian rhythms and pave the way to uncover molecular mechanisms
triggering pathological states associated to circadian misalignment.
Filiaciones:
Pacheco-Bernal I.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Biol Celular & Fisiol, Mexico City, DF, Mexico
Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Mexico City, Mexico
Becerril-Pérez F.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Biol Celular & Fisiol, Mexico City, DF, Mexico
Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Mexico City, Mexico
Aguilar-Arnal L.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Dept Biol Celular & Fisiol, Mexico City, DF, Mexico
Instituto de Investigaciones Biomédicas, Departamento de Biología Celular y Fisiología, Universidad Nacional Autónoma de México, Mexico City, Mexico
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