Densely ionizing radiation affects DNA methylation of selective LINE-1 elements

Sara Prior, Isabelle R. Miousse, Etienne Nzabarushimana, Rupak Pathak, Charles Skinner, Kristy R. Kutanzi, Antiño R. Allen, Jacob Raber, Alan J. Tackett, Martin Hauer-Jensen, Gregory A. Nelson, Igor Koturbash

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Long Interspersed Nucleotide Element 1 (LINE-1) retrotransposons are heavily methylated and are the most abundant transposable elements in mammalian genomes. Here, we investigated the differential DNA methylation within the LINE-1 under normal conditions and in response to environmentally relevant doses of sparsely and densely ionizing radiation. We demonstrate that DNA methylation of LINE-1 elements in the lungs of C57BL6 mice is dependent on their evolutionary age, where the elder age of the element is associated with the lower extent of DNA methylation. Exposure to 5-aza-2′-deoxycytidine and methionine-deficient diet affected DNA methylation of selective LINE-1 elements in an age- and promoter type-dependent manner. Exposure to densely IR, but not sparsely IR, resulted in DNA hypermethylation of older LINE-1 elements, while the DNA methylation of evolutionary younger elements remained mostly unchanged. We also demonstrate that exposure to densely IR increased mRNA and protein levels of LINE-1 via the loss of the histone H3K9 dimethylation and an increase in the H3K4 trimethylation at the LINE-1 5′-untranslated region, independently of DNA methylation. Our findings suggest that DNA methylation is important for regulation of LINE-1 expression under normal conditions, but histone modifications may dictate the transcriptional activity of LINE-1 in response to exposure to densely IR.

Original languageEnglish (US)
Pages (from-to)470-481
Number of pages12
JournalEnvironmental Research
Volume150
DOIs
StatePublished - Oct 1 2016

Fingerprint

Long Interspersed Nucleotide Elements
Ionizing radiation
methylation
DNA Methylation
Ionizing Radiation
DNA
decitabine
Histones
Histone Code
ionising radiation
Retroelements
DNA Transposable Elements
5' Untranslated Regions
Nutrition
Methionine
Dosimetry
genome
diet
Genes
Genome

Keywords

  • Epigenetics
  • High-LET radiation
  • Histone methylation
  • Ionizing radiation
  • Transposable elements

ASJC Scopus subject areas

  • Environmental Science(all)
  • Biochemistry

Cite this

Prior, S., Miousse, I. R., Nzabarushimana, E., Pathak, R., Skinner, C., Kutanzi, K. R., ... Koturbash, I. (2016). Densely ionizing radiation affects DNA methylation of selective LINE-1 elements. Environmental Research, 150, 470-481. https://doi.org/10.1016/j.envres.2016.06.043

Densely ionizing radiation affects DNA methylation of selective LINE-1 elements. / Prior, Sara; Miousse, Isabelle R.; Nzabarushimana, Etienne; Pathak, Rupak; Skinner, Charles; Kutanzi, Kristy R.; Allen, Antiño R.; Raber, Jacob; Tackett, Alan J.; Hauer-Jensen, Martin; Nelson, Gregory A.; Koturbash, Igor.

In: Environmental Research, Vol. 150, 01.10.2016, p. 470-481.

Research output: Contribution to journalArticle

Prior, S, Miousse, IR, Nzabarushimana, E, Pathak, R, Skinner, C, Kutanzi, KR, Allen, AR, Raber, J, Tackett, AJ, Hauer-Jensen, M, Nelson, GA & Koturbash, I 2016, 'Densely ionizing radiation affects DNA methylation of selective LINE-1 elements', Environmental Research, vol. 150, pp. 470-481. https://doi.org/10.1016/j.envres.2016.06.043
Prior S, Miousse IR, Nzabarushimana E, Pathak R, Skinner C, Kutanzi KR et al. Densely ionizing radiation affects DNA methylation of selective LINE-1 elements. Environmental Research. 2016 Oct 1;150:470-481. https://doi.org/10.1016/j.envres.2016.06.043
Prior, Sara ; Miousse, Isabelle R. ; Nzabarushimana, Etienne ; Pathak, Rupak ; Skinner, Charles ; Kutanzi, Kristy R. ; Allen, Antiño R. ; Raber, Jacob ; Tackett, Alan J. ; Hauer-Jensen, Martin ; Nelson, Gregory A. ; Koturbash, Igor. / Densely ionizing radiation affects DNA methylation of selective LINE-1 elements. In: Environmental Research. 2016 ; Vol. 150. pp. 470-481.
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