Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation

Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S. Turker, Jacob Raber

Research output: Research - peer-reviewArticle

Abstract

The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways. Significant overlap was observed between DNA methylation changes at the 2 and 20-week time points demonstrating specificity and retention of changes in response to radiation. Moreover, a novel class of DNA methylation change was observed following an environmental challenge (i.e. space irradiation), characterized by both increased and decreased 5hmC levels along the entire gene body. These changes were mapped to genes encoding neuronal functions including postsynaptic gene ontology categories. Thus, the brain's response to proton irradiation is both specific and prolonged and involves novel remodeling of non-random regions of the epigenome.

LanguageEnglish (US)
Article number10227
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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DNA Methylation
Epigenomics
Protons
Gene Ontology
Brain
Genes
Retention (Psychology)
Astronauts
Whole-Body Irradiation
Cytosine
Transcriptome
Methylation
Hippocampus
Radiation
Neoplasms
Therapeutics
Spatial Memory
Recognition (Psychology)
Radiation Exposure

ASJC Scopus subject areas

  • General

Cite this

Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation. / Impey, Soren; Jopson, Timothy; Pelz, Carl; Tafessu, Amanuel; Fareh, Fatema; Zuloaga, Damian; Marzulla, Tessa; Riparip, Lara Kirstie; Stewart, Blair; Rosi, Susanna; Turker, Mitchell S.; Raber, Jacob.

In: Scientific Reports, Vol. 7, No. 1, 10227, 01.12.2017.

Research output: Research - peer-reviewArticle

Impey, S, Jopson, T, Pelz, C, Tafessu, A, Fareh, F, Zuloaga, D, Marzulla, T, Riparip, LK, Stewart, B, Rosi, S, Turker, MS & Raber, J 2017, 'Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation' Scientific Reports, vol 7, no. 1, 10227. DOI: 10.1038/s41598-017-09191-4
Impey S, Jopson T, Pelz C, Tafessu A, Fareh F, Zuloaga D et al. Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation. Scientific Reports. 2017 Dec 1;7(1). 10227. Available from, DOI: 10.1038/s41598-017-09191-4
Impey, Soren ; Jopson, Timothy ; Pelz, Carl ; Tafessu, Amanuel ; Fareh, Fatema ; Zuloaga, Damian ; Marzulla, Tessa ; Riparip, Lara Kirstie ; Stewart, Blair ; Rosi, Susanna ; Turker, Mitchell S. ; Raber, Jacob. / Bi-directional and shared epigenomic signatures following proton and 56Fe irradiation. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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