%0 Journal Article %T The TGFB2-AS1 lncRNA Regulates TGF-beta Signaling by Modulating Corepressor Activity %+ Nutrition, Métabolismes et Cancer (NuMeCan) %+ Uppsala Universitet [Uppsala] %+ Harvard Medical School [Boston] (HMS) %A Papoutsoglou, Panagiotis %A Tsubakihara, Yutaro %A Caja, Laia %A Moren, Anita %A Pallis, Paris %A Ameur, Adam %A Heldin, Carl-Henrik %A Moustakas, Aristidis %Z Swedish Cancer SocietySwedish Cancer Society [CAN2015/438] %Z Swedish Research CouncilSwedish Research Council [K2013-66X-14936-10-5, 2015-02757] %Z European Research CouncilEuropean Research Council (ERC) [787472] %Z Bodossaki Foundation %Z Alexander Onassis Foundation %Z Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science %Z Kanae Foundation for the Promotion of Medical Science %Z Ludwig Cancer Research (Uppsala Branch) %< avec comité de lecture %@ 2211-1247 %J Cell Reports %I Elsevier Inc %V 28 %N 12 %P 3182-+ %8 2019-09 %D 2019 %R 10.1016/j.celrep.2019.08.028 %M 31533040 %K EED %K EZH2 %K PRC2 %K SUZ12 %K Smad %K TGF-β %K corepressor %K lncRNA %K signal transduction %K transcription %K tumor suppression %Z Life Sciences [q-bio]Journal articles %X Molecular processes involving lncRNAs regulate cell function. By applying transcriptomics, we identify lncRNAs whose expression is regulated by transforming growth factor beta (TGF-beta). Upon silencing individual lncRNAs, we identify several that regulate TGF-beta signaling. Among these lncRNAs, TGFB2-antisense RNA1 (TGFB2-AS1) is induced by TGF-beta through Smad and protein kinase pathways and resides in the nucleus. Depleting TGFB2-AS1 enhances TGF-beta/Smad-mediated transcription and expression of hallmark TGF-beta-target genes. Increased dose of TGFB2-AS1 reduces expression of these genes, attenuates TGF-beta-induced cell growth arrest, and alters BMP and Wnt pathway gene profiles. Mechanistically, TGFB2-AS1, mainly via its 3' terminal region, binds to the EED adaptor of the Polycomb repressor complex 2 (PRC2), promoting repressive histone H3K27me(3) modifications at TGF-beta-target gene promoters. Silencing EED or inhibiting PRC2 methylation activity partially rescues TGFB2-AS1-mediated gene repression. Thus, the TGF-beta-induced TGFB2-AS1 lncRNA exerts inhibitory functions on TGF-beta/BMP signaling output, supporting auto-regulatory negative feedback that balances TGF-beta/BMP-mediated responses. %G English %2 https://univ-rennes.hal.science/hal-02363311/document %2 https://univ-rennes.hal.science/hal-02363311/file/2019_Papoutsoglou_Cell%20Reports_1.pdf %L hal-02363311 %U https://univ-rennes.hal.science/hal-02363311 %~ INSERM %~ UNIV-RENNES1 %~ INRA %~ STATS-UR1 %~ NUMECAN %~ UR1-UFR-SVE %~ UR1-HAL %~ UR1-SDV %~ AGREENIUM %~ TEST-UR-CSS %~ UNIV-RENNES %~ UR1-BIO-SA