Long non-coding RNAs (lncRNAs) are implicated in a plethora of cellular processes, but an in-depth understanding of their functional features or their mechanisms of action is currently lacking. Here we study Meteor, a lncRNA transcribed near the gene encoding EOMES, a pleiotropic transcription factor implicated in various processes throughout development and in adult tissues. Using a wide array of perturbation techniques, we show that transcription elongation through the Meteor locus is required for Eomes activation in mouse embryonic stem cells, with Meteor repression linked to a change in the subpopulation primed to differentiate to the mesoderm lineage. We further demonstrate that a distinct functional feature of the locus-namely, the underlying DNA element-is required for suppressing Eomes expression following neuronal differentiation. Our results demonstrate the complex regulation that can be conferred by a single locus and emphasize the importance of careful selection of perturbation techniques when studying lncRNA loci.
Keywords: CP: Developmental biology; CP: Molecular biology; long non-coding RNAs, lncRNAs, embryonic stem cells, pluripotency, differentiation, EOMES.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.