Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Abstract

Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.

Double-bromo and extraterminal (BET) domain proteins regulate dendrite morphology and mechanosensory function

“…Previous structural studies have shown that the bromodomains of BET family proteins form a hydrophobic pocket enveloping acetylated histone tails (Umehara et al 2010a,b). Moreover, histone acetylation is largely, but not exclusively, regarded as a mark for transcriptional activation (Maze et al 2013). Therefore, fs(1)h may be required for transcriptional activation of gene expression, which has been shown in vitro with respect to Ubx (Chang et al 2007).…”

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

“…The phosphorylation or acetylation of histones is associated with the initiation of gene transcription, whereas the methylation of DNA is generally associated with the repression of gene transcription (Berger, 2007). Importantly, in neuronal cells, extracellular signals can impact epigenetic mechanisms through Ca 2+ signals, the translocation of ERK or other soluble cytosolic proteins to the nucleus (Cohen and Greenberg, 2008;Jordan and Kreutz, 2009;Day and Sweatt, 2011;Maze et al, 2013). Indeed, epigenetic mechanisms are now thought to play a critical role in the formation and consolidation of memory and other cognitive functions (Cohen and Greenberg, 2008;Jordan and Kreutz, 2009;Sweatt, 2010, 2011;Maze et al, 2013).…”

Molecular Pathways: Epigenetic Modulation of Wnt–Glycogen Synthase Kinase-3 Signaling to Target Human Cancer Stem Cells

“…As dopamine receptors and the associated signaling cascade were recently linked to CSCs (58), new insights into the histone methyltransferase G9a suggest a role for such a chromatin writer as a downstream effector of this pathway. Psychoactive drugs are known to have a major impact on neuron epigenetic landscapes and are likely to have similar effects on CSCs (59). Notably, antidepressants, repeated cocaine administration, and dopamine receptor signaling were all linked to G9a deregulation and aberrant H3K9 methylation patterning (60)(61)(62).…”