Regional Preferences of DNA Methylation Changes in Response to X-Ray Irradiation

Zielsetzung:

DNA methylation is involved in a broad spectrum of biological processes. We aimed to find epigenetic alterations caused by X-ray irradiation which could cause disturbances of the dynamic interplay of methylation and demethylation and possibly result in deregulated gene expression and promote genomic instability.

Material und Methoden:

In this study we employed methylated DNA-Immunoprecipitation in combination with genome wide and region specific DNA microarrays to identify irradiation induced changes of DNA methylation in response to X-ray irradiation in the lymphoblastoid cell line GM12878 and the primary lung fibroblast cell line IMR90.

Ergebnisse:

Although, cell type specific characteristics accounted for most of the differences within the detected DNA methylation profiles, radiation associated changes sufficed to separate exposed and unexposed samples of IMR90 by means of unsupervised hierarchical clustering. Furthermore, hypomethylated regions in IMR90 were characterized by significant overrepresentation of binding sites for NRF1, a transcription factor involved in oxidative stress response, and histone modification H3K36me3, which is known to be functionally associated with gene bodies and DNA methyltransferase 3b.

Schlussfolgerungen:

This biased distribution of DNA methylation changes might impact regional vulnerability to irradiation induced DNA double strand breaks. Understanding the underlying mechanisms will provide insights into the immediate and long term effects of irradiation on the epigenome

No conflict of interest has been declared by the author(s).