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In this article, a team of IBITECS (SBIGeM) contributed to the analysis of strand-specific transcriptome
changes during oncogene-induced human senescence.
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, are analyzed 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 intrans 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.
Figure legend: Cis- and Trans-chromatin modifications upon induction of senescence and expression of VAD.
Lazorthes S, Vallot C, Briois S, Aguirrebengoa M, Thuret JY, St Laurent G, Rougeulle C, Kapranov P, Mann C, Trouche D, Nicolas E. (2015). A vlincRNA participates in senescence maintenance by relieving H2AZ-mediated repression at the INK4 locus Nat. Commun.. 6, 5971 http://dx.doi.org/10.1038/ncomms6971
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.