AUTHOR=Gibbons Hunter R. , Shaginurova Guzel , Kim Laura C. , Chapman Nathaniel , Spurlock Charles F. , Aune Thomas M. 

TITLE=Divergent lncRNA GATA3-AS1 Regulates GATA3 Transcription in T-Helper 2 Cells

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02512

DOI=10.3389/fimmu.2018.02512

ISSN=1664-3224

ABSTRACT=<p>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. <italic>GATA3-AS1</italic> is a divergent lncRNA gene neighboring <italic>GATA3</italic>. 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 <italic>GATA3-AS1</italic> lncRNA is selectively expressed under TH2 polarizing conditions and is necessary for efficient transcription of <italic>GATA3, IL5</italic>, and <italic>IL13</italic> genes, while being sufficient for <italic>GATA3</italic> transcription. <italic>GATA3-AS1</italic> is required for formation of permissive chromatin marks, H3K27 acetylation and H3K4 di/tri-methylation, at the <italic>GATA3-AS1-GATA3</italic> locus. Further, <italic>GATA3-AS1</italic> 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.</p>