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Nat Immunol. 2015 Mar;16(3):318-325. doi: 10.1038/ni.3093. Epub 2015 Jan 26.

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

Author information

1
Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
2
IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
#
Contributed equally

Abstract

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 TH1 subset of helper T cells, was inversely correlated with expression of MAF, a TH2-associated transcription factor. Downregulation of linc-MAF-4 skewed T cell differentiation toward the TH2 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.

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PMID:
25621826
PMCID:
PMC4333215
DOI:
10.1038/ni.3093
[Indexed for MEDLINE]
Free PMC Article

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