Abstract
BackgroundGenetic, pharmacological, and environmental interventions that alter total levels of histone acetylation in specific brain regions can modulate behaviors and treatment responses. Efforts have been made to identify specific genes that are affected by alterations in total histone acetylation and to propose that such gene specific modulation could explain the effects of total histone acetylation levels on behavior — the implication being that under naturalistic conditions variability in histone acetylation occurs primarily around the promoters of specific genes.Methods/ResultsHere we challenge this hypothesis by demonstrating with a novel flow cytometry based technique that normal variability in open field exploration, a hippocampus-related behavior, was associated with total levels of histone acetylation in the hippocampus but not in other brain regions.ConclusionsResults suggest that modulation of total levels of histone acetylation may play a role in regulating biological processes. We speculate in the discussion that endogenous regulation of total levels of histone acetylation may be a mechanism through which organisms regulate cellular plasticity. Flow cytometry provides a useful approach to measure total levels of histone acetylation at the single cell level. Relating such information to behavioral measures and treatment responses could inform drug delivery strategies to target histone deacetylase inhibitors and other chromatin modulators to places where they may be of benefit while avoiding areas where correction is not needed and could be harmful.
Highlights
Chromatin organization is a tightly regulated process important for gene expression regulation[1,2]
Detection of histone H3 acetylation by flow cytometry Based on previous evidence within inbred mice linking largescale changes in the hippocampal transcriptome to behavior in the open-field (OF) test[12], we decided to determine possible epigenetic correlates of OF behavior by examining total levels of histone acetylation (AcH) throughout the genome using flow cytometry
While both procedures require immuolabeling, Western blotting is performed on protein extracts, whereas flow cytometry is performed on cells
Summary
Chromatin organization is a tightly regulated process important for gene expression regulation[1,2]. With respect to maternal care, rodent pups exposed to low levels of maternal care exhibited behavioral changes in adulthood that were reversed following treatment with histone deacetylase inhibitors (HDACi), compounds that increase total levels of AcH throughout the genome[6,7]. It was unclear from these studies whether modulation of total AcH acted as a blunt intervention which elicited biologically important specific effects at certain genes and non-specific effects at many others, or whether regulation of total AcH is an important biological process in itself. Efforts have been made to identify specific genes that are affected by alterations in total histone acetylation and to propose that such gene specific modulation could explain the effects of total histone acetylation levels on behavior — the implication being that under naturalistic conditions variability in histone acetylation occurs primarily around the promoters of specific genes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
