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Int. J. Mol. Sci. 2017, 18(7), 1430; doi:10.3390/ijms18071430

Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation

1
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
2
Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
3
Department of Bioinformatics, School of Informatics and Computing, Indiana University, Bloomington, IN 47408, USA
4
Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
5
Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
*
Author to whom correspondence should be addressed.
Received: 7 June 2017 / Revised: 28 June 2017 / Accepted: 30 June 2017 / Published: 4 July 2017
(This article belongs to the Special Issue DNA Methylation)
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Abstract

Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons are the major repetitive elements in mammalian genomes. LINE-1s are well-accepted as driving forces of evolution and critical regulators of the expression of genetic information. Alterations in LINE-1 DNA methylation may lead to its aberrant activity and are reported in virtually all human cancers and in experimental carcinogenesis. In this study, we investigated the endogenous DNA methylation status of the 5′ untranslated region (UTR) of LINE-1 elements in the bone marrow hematopoietic stem cells (HSCs), hematopoietic progenitor cells (HPCs), and mononuclear cells (MNCs) in radioresistant C57BL/6J and radiosensitive CBA/J mice and in response to ionizing radiation (IR). We demonstrated that basal levels of DNA methylation within the 5′-UTRs of LINE-1 elements did not differ significantly between the two mouse strains and were negatively correlated with the evolutionary age of LINE-1 elements. Meanwhile, the expression of LINE-1 elements was higher in CBA/J mice. At two months after irradiation to 0.1 or 1 Gy of 137Cs (dose rate 1.21 Gy/min), significant decreases in LINE-1 DNA methylation in HSCs were observed in prone to radiation-induced carcinogenesis CBA/J, but not C57BL/6J mice. At the same time, no residual DNA damage, increased ROS, or changes in the cell cycle were detected in HSCs of CBA/J mice. These results suggest that epigenetic alterations may potentially serve as driving forces of radiation-induced carcinogenesis; however, future studies are needed to demonstrate the direct link between the LINE-1 DNA hypomethylation and radiation carcinogenesis. View Full-Text
Keywords: DNA methylation; hematopoietic cells; ionizing radiation; retrotransposons DNA methylation; hematopoietic cells; ionizing radiation; retrotransposons
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MDPI and ACS Style

Miousse, I.R.; Chang, J.; Shao, L.; Pathak, R.; Nzabarushimana, É.; Kutanzi, K.R.; Landes, R.D.; Tackett, A.J.; Hauer-Jensen, M.; Zhou, D.; Koturbash, I. Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation. Int. J. Mol. Sci. 2017, 18, 1430.

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