Inter-Strain differences in LINE-1 DNA methylation in the mouse hematopoietic system in response to exposure to ionizing radiation

Isabelle R. Miousse, Jianhui Chang, Lijian Shao, Rupak Pathak, Étienne Nzabarushimana, Kristy R. Kutanzi, Reid D. Landes, Alan J. Tackett, Martin Hauer-Jensen, Daohong Zhou, Igor Koturbash

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 50 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 50-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 of137Cs (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.

Original languageEnglish (US)
Article number1430
JournalInternational journal of molecular sciences
Volume18
Issue number7
DOIs
StatePublished - Jul 4 2017
Externally publishedYes

Keywords

  • DNA methylation
  • Hematopoietic cells
  • Ionizing radiation
  • Retrotransposons

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Inter-Strain differences in LINE-1 DNA methylation in the mouse hematopoietic system in response to exposure to ionizing radiation'. Together they form a unique fingerprint.

Cite this