Histone Acetylation Maps in Aged Mice Developmentally Exposed to Lead: Epigenetic Drift and Alzheimer-Related Genes

Abstract

Aim: Early life exposure to lead (Pb) has been shown to increase late life biomarkers involved in Alzheimer’s disease (AD) pathology. Here, we tested the hypothesis that latent over expression of AD-related genes may be regulated through histone activation pathways. Methods: Chromatin immunoprecipitation sequencing was used to map the histone activation mark (H3K9Ac) to the mouse genome in developmentally Pb exposed mice on postnatal days 20, 270 and 700. Results: Exposure to Pb resulted in a global downregulation of H3K9Ac across the lifespan; except in genes associated with the Alzheimer pathway. Discussion: Early life exposure to Pb results in an epigenetic drift in H3K9Ac consistent with latent global gene repression. Alzheimer-related genes do not follow this trend.

Keywords::

• Alzheimer’s disease
• epigenetics
• histone acetylation
• lead (Pb)

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: https://www.tandfonline.com/doi/suppl/10.2217/epi-2017-0143

Acknowledgements

The authors would like to thank C Schorl of Brown University for his oversight and guidance with the DNA library preparation and B Renehan of the Ryan Institute at URI for advice and support given to A Eid.

Financial & competing interests disclosure

This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and by grant 5RO1ES015867-03. This research is based in part upon work conducted using the Rhode Island IDeA Network for Excellence in Biomedical Research Bioinformatics Core which is supported by the NIH under grant 2P20GM103430. JM Gaspar and RP Hart were supported by NIH grants 1R01AT009152 to A-N Kong of Rutgers University and 1R01ES026057 and R21DA035594 to RP Hart. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and by grant 5RO1ES015867-03. This research is based in part upon work conducted using the Rhode Island IDeA Network for Excellence in Biomedical Research Bioinformatics Core which is supported by the NIH under grant 2P20GM103430. JM Gaspar and RP Hart were supported by NIH grants 1R01AT009152 to A-N Kong of Rutgers University and 1R01ES026057 and R21DA035594 to RP Hart. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.