A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus

Sandra Lazorthes, Céline Vallot, Sébastien Briois, Marion Aguirrebengoa, Jean-Yves Thuret, Georges St. Laurent, Claire Rougeulle, Philipp Kapranov, Carl Mann, Didier Trouche and Estelle Nicolas ()
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Sandra Lazorthes: Université de Toulouse; UPS; LBCMCP
Céline Vallot: UMR 7216, Université Paris Diderot
Sébastien Briois: Université de Toulouse; UPS; LBCMCP
Marion Aguirrebengoa: Université de Toulouse; UPS; LBCMCP
Jean-Yves Thuret: CEA, iBiTec-S, SBIGeM/CNRS-FRE3377 and I2BC/Université Paris-Sud and Paris-Saclay
Georges St. Laurent: St Laurent Institute
Claire Rougeulle: UMR 7216, Université Paris Diderot
Philipp Kapranov: St Laurent Institute
Carl Mann: CEA, iBiTec-S, SBIGeM/CNRS-FRE3377 and I2BC/Université Paris-Sud and Paris-Saclay
Didier Trouche: Université de Toulouse; UPS; LBCMCP
Estelle Nicolas: Université de Toulouse; UPS; LBCMCP

Nature Communications, 2015, vol. 6, issue 1, 1-16

Abstract: Abstract Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process and a major anticancer barrier, is associated with dramatic chromatin reorganization in heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed RNAs are mostly repressed during senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class are mainly activated. We show that VAD, a novel antisense vlincRNA strongly induced during senescence, is required for the maintenance of senescence features. VAD modulates chromatin structure in cis and activates gene expression in trans at the INK4 locus, which encodes cell cycle inhibitors important for senescence-associated cell proliferation arrest. Importantly, VAD inhibits the incorporation of the repressive histone variant H2A.Z at INK4 gene promoters in senescent cells. Our data underline the importance of vlincRNAs as sensors of cellular environment changes and as mediators of the correct transcriptional response.

Date: 2015
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DOI: 10.1038/ncomms6971

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