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

Valeria Ranzani, Grazisa Rossetti, Ilaria Panzeri, Alberto Arrigoni, Raoul J P Bonnal, Serena Curti, Paola Gruarin, Elena Provasi, Elisa Sugliano, Maurizio Marconi, Raffaele De Francesco, Jens Geginat, Beatrice Bodega, Sergio Abrignani, Massimiliano Pagani

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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 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.

Original languageEnglish
Pages (from-to)318-325
Number of pages8
JournalNature Immunology
Volume16
Issue number3
DOIs
Publication statusPublished - Feb 17 2015

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ASJC Scopus subject areas

  • Immunology

Cite this

Ranzani, V., Rossetti, G., Panzeri, I., Arrigoni, A., Bonnal, R. J. P., Curti, S., Gruarin, P., Provasi, E., Sugliano, E., Marconi, M., De Francesco, R., Geginat, J., Bodega, B., Abrignani, S., & Pagani, M. (2015). The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nature Immunology, 16(3), 318-325. https://doi.org/10.1038/ni.3093