AbstractPolycomb Repressive Complex 2 (PRC2) is an epigenetic regulator required for gene silencing during development. Although PRC2 is a well-established RNA-binding complex, the biological function of PRC2-RNA interaction has been controversial. Here, we study the gene-regulatory role of the inhibitory PRC2-RNA interactions. We report a nuclear long non-coding RNA,LEVER, which mapped 236 kb upstream of theβ-globincluster as confirmed by Nanopore sequencing.LEVERRNA interacts with PRC2 in its nascent form, and this prevents the accumulation of the H3K27 repressive histone marks withinLEVERlocus. Interestingly, the accessibleLEVERchromatin, in turn, suppresses the chromatin interactions between theε-globinlocus andβ-globinlocus control region (LCR), resulting in a repressive effect onε-globingene expression. Our findings validate that the nascent RNA-PRC2 interaction inhibits local PRC2 function in situ. More importantly, we demonstrate that such a local process can in turn regulate the expression of neighboring genes.