title: Neuron-specific chromatin remodeling: a missing link in epigenetic mechanisms underlying synaptic plasticity, memory, and intellectual disability disorders.
abstract: Long-term memory formation requires the coordinated regulation of gene expression. Until recently nucleosome remodeling, one of the major epigenetic mechanisms for controlling gene expression, had been largely unexplored in the field of neuroscience. Nucleosome remodeling is carried out by chromatin remodeling complexes (CRCs) that interact with DNA and histones to physically alter chromatin structure and ultimately regulate gene expression. Human exome sequencing and gene wide association studies have linked mutations in CRC subunits to intellectual disability disorders, autism spectrum disorder and schizophrenia. However, how mutations in CRC subunits were related to human cognitive disorders was unknown. There appears to be both developmental and adult specific roles for the neuron specific CRC nBAF (neuronal Brg1/hBrm Associated Factor). nBAF regulates gene expression required for dendritic arborization during development, and in the adult, contributes to long-term potentiation, a form of synaptic plasticity, and long-term memory. We propose that the nBAF complex is a novel epigenetic mechanism for regulating transcription required for long-lasting forms of synaptic plasticity and memory processes and that impaired nBAF function may result in human cognitive disorders.
authors.affiliation: University of California, Irvine, Department of Neurobiology & Behavior, Irvine, CA, USA; Center for the Neurobiology of Learning & Memory, Irvine, CA, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Vogel-Ciernia
authors.affiliation: University of California, Irvine, Department of Neurobiology & Behavior, Irvine, CA, USA; Center for the Neurobiology of Learning & Memory, Irvine, CA, USA. Electronic address: mwood@uci.edu.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology*; D008568:Memory; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008954:Models, Biological; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000201:enzymology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C467332:ACTL6B protein, human; D000199:Actins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C084011:SMARCA2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: Autism spectrum disorder; Chromatin remodeling; Epigenetics; Intellectual disability disorder; Long-term memory; Long-term potentiation; Nucleosome remodeling