The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4

• Published in: Nature immunology Vol. 16; no. 3; pp. 318 - 325
• Main Authors: Ranzani, Valeria, Rossetti, Grazisa, Panzeri, Ilaria, Arrigoni, Alberto, Bonnal, Raoul J P, Curti, Serena, Gruarin, Paola, Provasi, Elena, Sugliano, Elisa, Marconi, Maurizio, De Francesco, Raffaele, Geginat, Jens, Bodega, Beatrice, Abrignani, Sergio, Pagani, Massimiliano
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-03-2015; Nature Publishing Group
• Subjects: 38/109; 38/77; 38/89; 631/250/2502/2170; 96/31; Biomedicine; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Down-Regulation - genetics; Down-Regulation - immunology; Humans; Immune system; Immunology; Infectious Diseases; Lymphocytes; Maf Transcription Factors - genetics; Maf Transcription Factors - immunology; Physiological aspects; resource; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - immunology; T cells; T-Lymphocytes - immunology; Transcription, Genetic - genetics; Transcription, Genetic - immunology; Transcriptome - genetics; Transcriptome - immunology
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.3093

Long intergenic noncoding RNAs (lincRNAs) contribute to the regulation of gene expression. Pagani and colleagues identify hundreds of unique lincRNAs expressed in human lymphocytes and demonstrate a role for the lincRNA linc-MAF-4 in the differentiation of CD4
+
T cells.
Long noncoding RNAs are emerging as important regulators of cellular functions, but little is known of their role in the human immune system. Here we investigated long intergenic noncoding RNAs (lincRNAs) in 13 subsets of T lymphocytes and B lymphocytes by next-generation sequencing–based RNA sequencing (RNA-seq analysis) and
de novo
transcriptome reconstruction. We identified over 500 previously unknown lincRNAs and described lincRNA signatures. Expression of linc-MAF-4, a chromatin-associated lincRNA specific to the T
H
1 subset of helper T cells, was inversely correlated with expression of MAF, a T
H
2-associated transcription factor. Downregulation of linc-MAF-4 skewed T cell differentiation toward the T
H
2 phenotype. We identified a long-distance interaction between the genomic regions of the gene encoding linc-MAF-4 and
MAF
, where linc-MAF-4 associated with the chromatin modifiers LSD1 and EZH2; this suggested that linc-MAF-4 regulated
MAF
transcription through the recruitment of chromatin modifiers. Our results demonstrate a key role for lincRNA in T lymphocyte differentiation.