Previously we analysed the epigenomic differences between various T helper cells. The mammalian genomes encode tens of thousands of long noncoding RNAs (lncRNA). These transcripts play essential roles in regulating gene expression and affect various biological processes during development and in pathological conditions. The study of lincRNA function in the immune system is an emerging field. T helper (TH) cells are critical for orchestrating adaptive immune responses to a variety of pathogens; they are also involved in the pathogenesis of different types of immunological diseases including allergy, asthma and autoimmunity. In our recent studies, we have investigated histone modification enzymes in the differentiation of T helper cells. To better understand the role of lincRNAs in the development and differentiation of T cell lineages, we performed RNA-seq of 42 subsets of thymocytes and mature peripheral T cells at multiple time points during their differentiation. Analysis of this dataset identified 1,524 genomic regions that generate lincRNAs. Our data reveal a highly dynamic and cell- or stage-specific pattern of lincRNA expression. Genomic location analysis of the lincRNA genes revealed that they are adjacent to protein-coding genes critically involved in regulating immune function, suggesting a possible co-evolution of protein-coding and lincRNA genes. Using gene deficient mice, we found that the transcription factors T-bet, GATA-3, STAT4 and STAT6 account for the cell-specific expression of most lincRNAs in TH1 and TH2 cells. Inhibition of a TH2-specific lincRNA, LincR-Ccr2-5'AS, whose expression is regulated by GATA-3, by shRNA resulted in deregulation of numerous genes preferentially expressed in TH2 cells including several chemokine receptor genes that reside in the vicinity of the LincR-Ccr2-5'AS and compromised TH2 migration to lung tissues in mice. We provide a comprehensive resource for studying the function and mechanisms of lincRNA in T cell development, differentiation and immune response. Our recent studies indicate that the enzymes that regulate histone methylation are critically involved in the differentiation of T helper cells.
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