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Nat Commun. 2015 Jan 20;6:5971. doi: 10.1038/ncomms6971.

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

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1] Université de Toulouse; UPS; LBCMCP; F-31062 Toulouse, France [2] CNRS; LBCMCP; F-31062 Toulouse, France.
UMR 7216, Université Paris Diderot, 75205 Paris, France.
CEA, iBiTec-S, SBIGeM/CNRS-FRE3377 and I2BC/Université Paris-Sud and Paris-Saclay, 91191 Gif-sur-Yvette, France.
St Laurent Institute, Woburn, Massachusetts 01801, USA.
1] St Laurent Institute, Woburn, Massachusetts 01801, USA [2] Institute of Genomics, Huaqiao University School of Medicine, Xiamen 361021, China [3] Academy of Biology and Biotechnology, South Federal University, Rostov-on-Don, Russia.


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.

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