title: Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease.
abstract: In postmitotic neurons, nucleosomal turnover was long considered to be a static process that is inconsequential to transcription. However, our recent studies in human and rodent brain indicate that replication-independent (RI) nucleosomal turnover, which requires the histone variant H3.3, is dynamic throughout life and is necessary for activity-dependent gene expression, synaptic connectivity, and cognition. H3.3 turnover also facilitates cellular lineage specification and plays a role in suppressing the expression of heterochromatic repetitive elements, including mutagenic transposable sequences, in mouse embryonic stem cells. In this essay, we review mechanisms and functions for RI nucleosomal turnover in brain and present the hypothesis that defects in histone dynamics may represent a common mechanism underlying neurological aging and disease.
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Wenderski
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Maze
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D042002:Chromatin Assembly and Disassembly; D020077:Endogenous Retroviruses / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D051379:Mice; D008938:Mitosis; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D020086:Short Interspersed Nucleotide Elements; D014158:Transcription, Genetic
chemical_list: D006570:Heterochromatin; D006657:Histones; D009707:Nucleosomes; D063151:Polycomb Repressive Complex 2
keywords: H3.3; aging; histone variant; neurological disease; nucleosomal turnover; replication-independent