title: The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4.
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.
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ranzani
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Grazisa
authors.initials: G
authors.lastname: Rossetti
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Panzeri
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Arrigoni
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Raoul Jp
authors.initials: RJ
authors.lastname: Bonnal
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Curti
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Gruarin
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Provasi
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sugliano
authors.affiliation: IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marconi
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Francesco
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Jens
authors.initials: J
authors.lastname: Geginat
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bodega
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abrignani
authors.affiliation: Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", 20122 Milano, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pagani
mesh_terms: D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D050977:Maf Transcription Factors / Q000235:genetics* / Q000276:immunology; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology; D059467:Transcriptome / Q000235:genetics / Q000276:immunology
chemical_list: D050977:Maf Transcription Factors; D062085:RNA, Long Noncoding