Format

Send to

Choose Destination
Bioessays. 2016 May;38(5):410-9. doi: 10.1002/bies.201500171. Epub 2016 Mar 15.

Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease.

Author information

1
Department of Developmental Biology, Stanford University, Stanford, CA, USA.
2
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

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.

KEYWORDS:

H3.3; aging; histone variant; neurological disease; nucleosomal turnover; replication-independent

PMID:
26990528
PMCID:
PMC4968875
DOI:
10.1002/bies.201500171
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center