Deciphering the role of regulatory noncoding RNAs in human CD4+ T lymphocytes differentiation through functional and biochemical studies

Long non-coding-RNAs are emerging as important regulators of cellular functions but little is known on their role in human immune system. Here we investigated long intergenic non-coding-RNAs (lincRNAs) in TH1 lymphocyte subset. We focused on the TH1-specific lincRNA linc-MAF-4, whose gene is located ≈140 kb upstream MAF: a TH2-associated transcription factor. Linc-MAF-4 expression was found to anti-correlate with MAF. Also, down-regulation of linc-MAF-4 increases the expression of TH2-specific genes and skews T cell differentiation toward TH2 fate. Linc-MAF-4 is enriched in the chromatin fraction and thanks to a long-distance chromosome interaction between linc-MAF-4 and MAF genomic regions, linc-MAF-4 recruits LSD1 and EZH2 at MAF promoter to downregulate its transcription. These data demonstrate a key role of lincRNAs in human T lymphocyte differentiation.