title: Densely ionizing radiation affects DNA methylation of selective LINE-1 elements.
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.
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Prior
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Isabelle R
authors.initials: IR
authors.lastname: Miousse
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Department of Bioinformatics, School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Etienne
authors.initials: E
authors.lastname: Nzabarushimana
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Rupak
authors.initials: R
authors.lastname: Pathak
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Skinner
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Kristy R
authors.initials: KR
authors.lastname: Kutanzi
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Antiño R
authors.initials: AR
authors.lastname: Allen
authors.affiliation: Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Raber
authors.affiliation: Department of Biochemistry, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Tackett
authors.affiliation: Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
authors.affiliation: Department of Basic Sciences, Division of Radiation Research, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Nelson
authors.affiliation: Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: ikoturbash@uams.edu.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000528:radiation effects*; D000077209:Decitabine; D006657:Histones / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics* / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D011839:Radiation, Ionizing
chemical_list: D006657:Histones; D000077209:Decitabine; D001374:Azacitidine
keywords: Epigenetics; High-LET radiation; Histone methylation; Ionizing radiation; Transposable elements