Abstract:
: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. GATA3-AS1 is a divergent lncRNA gene neighboring GATA3. 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 GATA3-AS1 lncRNA is selectively expressed under TH2 polarizing conditions and is necessary for efficient transcription of GATA3, IL5, and IL13 genes, while being sufficient for GATA3 transcription. GATA3-AS1 is required for formation of permissive chromatin marks, H3K27 acetylation and H3K4 di/tri-methylation, at the GATA3-AS1-GATA3 locus. Further, GATA3-AS1 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.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Gibbons HR,Shaginurova G,Kim LC,Chapman N,Spurlock CF 3rd,Aune TMdoi
10.3389/fimmu.2018.02512subject
Has Abstractpub_date
2018-10-29 00:00:00pages
2512issn
1664-3224journal_volume
9pub_type
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02002
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doi:10.3389/fimmu.2018.01152
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pub_type: 杂志文章,评审
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