Long non-coding-RNAs are emerging as important regulators of cellular functions but little is known on their role in human immune system. Here we investigated long intergenic non-coding-RNAs (lincRNAs) in TH1 lymphocyte subset. We focused on the TH1-specific lincRNA linc-MAF-4, whose gene is located ≈140 kb upstream MAF: a TH2-associated transcription factor. Linc-MAF-4 expression was found to anti-correlate with MAF. Also, down-regulation of linc-MAF-4 increases the expression of TH2-specific genes and skews T cell differentiation toward TH2 fate. Linc-MAF-4 is enriched in the chromatin fraction and thanks to a long-distance chromosome interaction between linc-MAF-4 and MAF genomic regions, linc-MAF-4 recruits LSD1 and EZH2 at MAF promoter to downregulate its transcription. These data demonstrate a key role of lincRNAs in human T lymphocyte differentiation.

Deciphering the role of regulatory noncoding RNAs in human CD4+ T lymphocytes differentiation through functional and biochemical studies

PANZERI, ILARIA
2014

Abstract

Long non-coding-RNAs are emerging as important regulators of cellular functions but little is known on their role in human immune system. Here we investigated long intergenic non-coding-RNAs (lincRNAs) in TH1 lymphocyte subset. We focused on the TH1-specific lincRNA linc-MAF-4, whose gene is located ≈140 kb upstream MAF: a TH2-associated transcription factor. Linc-MAF-4 expression was found to anti-correlate with MAF. Also, down-regulation of linc-MAF-4 increases the expression of TH2-specific genes and skews T cell differentiation toward TH2 fate. Linc-MAF-4 is enriched in the chromatin fraction and thanks to a long-distance chromosome interaction between linc-MAF-4 and MAF genomic regions, linc-MAF-4 recruits LSD1 and EZH2 at MAF promoter to downregulate its transcription. These data demonstrate a key role of lincRNAs in human T lymphocyte differentiation.
12-dic-2014
Inglese
Università degli Studi di Milano-Bicocca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/105608
Il codice NBN di questa tesi è URN:NBN:IT:UNIMIB-105608