title: Escape of X-linked miRNA genes from meiotic sex chromosome inactivation.
abstract: Past studies have indicated that transcription of all X-linked genes is repressed by meiotic sex chromosome inactivation (MSCI) during the meiotic phase of spermatogenesis in mammals. However, more recent studies have shown an increase in steady-state levels of certain X-linked miRNAs in pachytene spermatocytes, suggesting that either synthesis of these miRNAs increases or that degradation of these miRNAs decreases dramatically in these cells. To distinguish between these possibilities, we performed RNA-FISH to detect nascent transcripts from multiple miRNA genes in various spermatogenic cell types. Our results show definitively that Type I X-linked miRNA genes are subject to MSCI, as are all or most X-linked mRNA genes, whereas Type II and III X-linked miRNA genes escape MSCI by continuing ongoing, active transcription in primary spermatocytes. We corroborated these results by co-localization of RNA-FISH signals with both a corresponding DNA-FISH signal and an immunofluorescence signal for RNA polymerase II. We also found that X-linked miRNA genes that escape MSCI locate non-randomly to the periphery of the XY body, whereas genes that are subject to MSCI remain located within the XY body in pachytene spermatocytes, suggesting that the mechanism of escape of X-linked miRNA genes from MSCI involves their relocation to a position outside of the repressive chromatin domain associated with the XY body. The fact that Type II and III X-linked miRNA genes escape MSCI suggests an immediacy of function of the encoded miRNAs specifically required during the meiotic stages of spermatogenesis.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Sosa
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Flores
authors.affiliation: Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA john.mccarrey@utsa.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: McCarrey
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis; D051379:Mice / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs; D013090:Spermatocytes / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic; D014960:X Chromosome / Q000378:metabolism; D049951:X Chromosome Inactivation; D014998:Y Chromosome / Q000378:metabolism
chemical_list: D035683:MicroRNAs
keywords: Epigenetic regulation; Germ cells; Male fertility; Meiosis; Spermatogenesis; X inactivation