Divergent lncRNA Regulates Transcription in T-Helper 2 Cells.

Long non-coding RNAs (lncRNAs) possess a diverse array of regulatory functions including activation and silencing of gene transcription, regulation of splicing, and coordinating epigenetic modifications. is a divergent lncRNA gene neighboring . GATA3 is considered the master regulator of TH2 lineage commitment enabling TH2 effector cells to efficiently transcribe genes encoding cytokines IL-4, IL-5, and IL-13. Here, we show that the lncRNA is selectively expressed under TH2 polarizing conditions and is necessary for efficient transcription of , and genes, while being sufficient for transcription. is required for formation of permissive chromatin marks, H3K27 acetylation and H3K4 di/tri-methylation, at the locus. Further, binds components of the MLL methyltransferase and forms a DNA-RNA hybrid (R-loop) thus tethering the MLL methyltransferase to the gene locus. Our results indicate a novel regulatory function for a divergent lncRNA and provide new insight into the function of lncRNAs in T helper cell differentiation.