LINE‐1 retrotransposon copies are amplified during murine early embryo development

Abstract

Two large families of retrotransposons, that is, LINE-1 (Long Interspersed Nuclear Elements-1) and endogenous retroviruses, encode reverse transcriptase (RT) proteins in vertebrates. We previously showed that mouse preimplantation embryos are endowed with an endogenous, functional RT activity. Inhibiting that activity by microinjecting antisense oligonucleotides against a highly active LINE-1 family member in mouse oocytes blocked developmental progression between the two- and four-blastomere stages, indicating that LINE-1-encoded RT activity is strictly required at this critical transition in early development. Here we show that incubation of mouse zygotes with 5'-bromodeoxyuridine (BrdU) yields massive incorporation of this nucleoside analogue in newly synthesized DNA; surprisingly, a significant incorporation still occurs in both zygotic pronuclei in the presence of aphidicolin, a specific inhibitor of DNA replication. This aphidicolin-resistant BrdU incorporation is quantitatively abolished when embryos are simultaneously exposed to abacavir, a nucleoside RT inhibitor, indicating its retrotranscription-dependent nature. Moreover, quantitative PCR analysis revealed a burst of new synthesis of LINE-1 copies at the zygote- and two-cell embryo stages. These findings support the conclusion that RT-dependent amplification of LINE-1 retrotransposons is a distinctive feature of early embryonic genomes. Its physiological involvement in preimplantation murine development is discussed.

Regulatory roles of LINE-1-encoded reverse transcriptase in cancer onset and progression

“…The data discussed in this review suggest that cancer is primarily linked to what used to be called “junk DNA”, i.e. the retrotransposon component of our genome, that played crucial roles in very early stages of our development [9, 78, 79, 94, 95, 96] and is subsequently silenced and kept inactive in differentiated tissues. Cancer can therefore be viewed as the unscheduled resurrection of an embryonic mechanism within an out-of-context differentiated environment and represent the closest product to an embryo that differentiated cells can generate.…”

“…The down-regulation of miRNAs in cancer cells shares striking similarities with the suppression of miRNA functions in early embryos [92], a naturally occurring phenomenon correlated with three concomitant events: massive reduction of the overall methyl-cytosine content in the embryonic genome [93],bursts of retrotransposon expression [94], andincreased activity of embryonic RT activity [95]. …”

Exposure to Low-Dose 56Fe-Ion Radiation Induces Long-Term Epigenetic Alterations in Mouse Bone Marrow Hematopoietic Progenitor and Stem Cells

“…LINE1 copy number was assessed as described in Vitullo et al (31). Briefly, LINE1 ORF1 was amplified by real-time quantitative PCR from 10 ng of gDNA.…”

Genopolitics and the Science of Genetics

“…Hence, these elements expand in number as they retrotranspose, leading to an increase in genomic DNA content and a change in DNA sequence and structure at the region of insertion (Faulkner 2011). For the most part, the activity of retrotransposons is epigenetically silenced due to potentially deleterious effects, but there are two critical exceptions: First, for a period during early embryogenesis, retrotransposons are released from epigenetic suppression and become active (Coufal et al 2009) and may influence the manner in which neural precursor cells differentiate to form distinct types of neurons in the embryo (Vitullo et al 2012); second, retrotransposition is ongoing in those parts of the brain (the hippocampus and the subventricular zone) that produce new neurons throughout life (Muotri et al 2010).…”