Developmental conservation of microRNA gene localization at the nuclear periphery

Abstract

microRNAs are of vital importance for the regulation of the adaptive and innate immune responses, modulating gene expression at the post transcriptional level. Although there is cumulative information regarding the steady state mature microRNA levels and their respective targets, little is known about the effect of the three-dimensional chromatin architecture on the transcriptional regulation of microRNA gene loci. Here, we sought to investigate the effect of subnuclear localization on the transcriptional activation of eight murine microRNA loci in the immune system. Our results show that microRNA genes display a preferential monoallelic gene expression profile accompanied with perinuclear localization irrespectively of their transcription status or differentiation state. The expression profile and perinuclear localization are developmentally conserved while microRNA gene loci localization outside constitutive lamin associated domains is cross-species conserved. Our findings provide support for an active nuclear periphery and its role in chromatin organization of the non-coding genome.