Complex regulation of Eomes levels mediated through distinct functional features of the Meteor long non-coding RNA locus

Long non-coding RNAs (lncRNAs) are implicated in a plethora of cellular processes, but an in-depth under-standing 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 em-bryonic 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.

Automated summary

This study investigates a lncRNA (Meteor) that is transcribed near the gene encoding EOMES and finds that transcription elongation through the Meteor locus is necessary for Eomes activation in mouse embryonic stem cells and is associated with mesoderm differentiation. The study also reveals that a distinct DNA element within the locus is required for suppressing Eomes expression following neuronal differentiation.