1. Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease.
- Author
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Wenderski W and Maze I
- Subjects
- Aging metabolism, Aging pathology, Animals, Brain growth & development, Brain metabolism, Brain pathology, Chromatin Assembly and Disassembly, Endogenous Retroviruses genetics, Endogenous Retroviruses metabolism, Heterochromatin chemistry, Heterochromatin metabolism, Histones genetics, Humans, Long Interspersed Nucleotide Elements, Mice, Mitosis, Mouse Embryonic Stem Cells cytology, Mouse Embryonic Stem Cells metabolism, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Neurons cytology, Nucleosomes chemistry, Nucleosomes metabolism, Polycomb Repressive Complex 2 genetics, Polycomb Repressive Complex 2 metabolism, Short Interspersed Nucleotide Elements, Aging genetics, Histones metabolism, Neurodegenerative Diseases genetics, Neurons metabolism, Transcription, Genetic
- 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., (© 2016 WILEY Periodicals, Inc.)
- Published
- 2016
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