Journal
ENVIRONMENTAL RESEARCH
Volume 150, Issue -, Pages 470-481Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.envres.2016.06.043
Keywords
Epigenetics; High-LET radiation; Histone methylation; Ionizing radiation; Transposable elements
Funding
- National Institute of Health Center of Biological Research Excellence [1P20GM109005]
- National Institute of Health [R21ES025268]
- National Aeronautics and Space Administration [NNX10AD59G, NNJ12ZSA001N]
- Arkansas Space Grant Consortium through National Aeronautics and Space Administration [NNX13AB29A]
- National Space Biomedical Research Institute through the National Aeronautics and Space Administration [NCC 9-58, RE03701]
- NIH/UAMS Clinical and Translational Science Award [UL1TR000039, KL2TR000063]
- Arkansas Biosciences Institute
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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. (C) 2016 Elsevier Inc. All rights reserved.
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