title: DNA damage-induced upregulation of miR-709 in the germline downregulates BORIS to counteract aberrant DNA hypomethylation.
abstract: MicroRNAs as potent regulators of gene expression are involved in spermatogenesis, yet their role in response of germline to genotoxic stress is obscure. We studied the microRNAome profile of X-ray irradiated mouse testes using the microarray technique. We found that radiation exposure significantly affected microRNA expression in testes. Mir-709 was the most abundant in both control and irradiated testes, and a big difference in miR-709 levels was observed between the control and exposed group. We found that miR-709 targets the Brother of the Regulator of Imprinted Sites (BORIS), an important regulator of DNA methylation and imprinting. Here, we for the first time show that the DNA damage-induced and ATR/Rfx1-mediated increase of miR-709 expression in exposed testes may be a protective mechanism that effectively decreases a cellular level of BORIS to prevent massive aberrant erasure of DNA methylation after radiation exposure.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Tamminga
authors.forename: Palak
authors.initials: P
authors.lastname: Kathiria
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D019175:DNA Methylation / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics* / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D013737:Testis / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D015854:Up-Regulation / Q000235:genetics* / Q000528:radiation effects; D014965:X-Rays
chemical_list: C499208:Ctcfl protein, mouse; D004268:DNA-Binding Proteins; D035683:MicroRNAs