No abstract

16Long non-coding RNAs (lncRNAs) have been well-established to act as regulators and mediators 17 of development and cell fate specification programs. LncRNA Mrhl (meiotic recombination 18 hotspot locus) has been shown to act in a negative feedback loop with WNT signaling to regulate 19 male germ cell meiotic commitment. In our current study, we have addressed the role of Mrhl in 20 development and differentiation using mouse embryonic stem cells (mESCs) as our model 21 system of study. We found Mrhl to be a nuclear-localized, chromatin-bound lncRNA with 22 moderately stable expression in mESCs. Transcriptome analyses and loss-of-function phenotype 23 studies revealed dysregulation of developmental processes and lineage-specific genes along with 24 aberrance in specification of early lineages during differentiation of mESCs. Genome-wide 25 chromatin occupancy studies suggest regulation of chromatin architecture at key target loci 26 through triplex formation. Our studies thus reveal a role for lncRNA Mrhl in regulating 27 differentiation programs in mESCs in the context of appropriate cues through chromatin-28 mediated responses. 29