Scientific Understanding of Consciousness
Chromatin Remodeling Regulates Neural Coding
Science 15 Jul 2016: Vol. 353, Issue 6296, pp. 300-305
Chromatin remodeling inactivates activity genes and regulates neural coding
Yue Yang, et.al.
Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA.
MD-PhD Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Neuronal activity influences transcription in neurons, and hence regulates neural circuits. Activity-dependent genes are often rapidly transcribed and then rapidly inactivated. However, attention has focused on the induction of transcription rather than the biological roles and mechanisms of inactivation of activity-dependent transcription.
Epigenetic regulators, including adenosine 5′-triphosphate (ATP)–dependent chromatin-remodeling enzymes, are ideally suited to orchestrate the effects of neuronal activity on transcription globally. The ATP-dependent nucleosome remodeling and deacetylase (NuRD) complex triggers alterations of histone modifications, resulting in promoter or enhancer decommissioning and prolonged silencing of transcription.
In behavior analyses, depletion of Chd4 in granule neurons impaired procedural learning, including in the accelerating rotarod and delay eyeblink conditioning assays, but had little or no effect on motor coordination as assessed in the DigiGait and open field assays.
Our study defines chromatin-remodeling events that inactivate activity-dependent transcription and control dendrite architecture and sensorimotor encoding in the brain. Our findings suggest that inactivation of activity genes is essential for the maturation of granule neuron dendrite arbors and in the control of neural circuit activity in response to sensorimotor signals. We have uncovered the NuRD complex and H2A.z as epigenetic regulators that mediate the inactivation of activity genes in the brain. Thus, epigenetic mechanisms may have an active role in the inactivation of gene expression in the brain following neuronal activity.
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