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.
Highlights
DNA methylation is one of the key epigenetic mechanisms that regulate the expression of genetic information [1]
In a recent study from our group, we reported that a pool of hematopoietic stem and progenitor cells (HSPCs) was more susceptible to epigenetic alterations than mononuclear cells (MNCs) [22]
In this study, we investigated the differences in the hematopoietic profiles of two mouse strains—the relatively radioresistant C57BL/6J and relatively radiosensitive CBA/J—under normal conditions and in response to ionizing radiation (IR)
Summary
DNA methylation is one of the key epigenetic mechanisms that regulate the expression of genetic information [1]. One of the major functions of DNA methylation is the regulation of transcriptional activity of the repetitive elements that comprise up to two-thirds of mammalian genomes. Evolutionary patterns of LINE-1 are characterized by the continuous replacement of extinct families by more recently evolved families, which predetermines substantial differences between the elements [9]. These differences primarily stem from the 5 -UTRs, and murine LINE-1s were recently classified according to each family’s unique 5 -UTR sequence and evolutionary age [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
