Implication of repeat insertion domains in the trans -activity of the long non-coding RNA ANRIL

Autor: Virginie Marchand, Isabelle Behm-Ansmant, Aymeric Sanchez, Christiane Branlant, Charbel Alfeghaly, Yuri Motorin, Valérie Igel-Bourguignon, Sylvain Maenner, Raphael Rouget, Quentin Thuillier
Přispěvatelé: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), French PIA project 'Lorraine Universite d’Excellence' ´[ANR-15-IDEX-04-LUE, in part], PIA RHU program FIGHT-HF [ANR-15-RHU-004], CNRS-UL and the FR3209 (renamed UMS2008-IBSLor) in the context of Action de Site Mirabelle and PEPS initiatives, respectively., IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), BEHM-ANSMANT, Isabelle, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nucleic Acids Research
Nucleic Acids Research, Oxford University Press, 2021, 49 (9), pp.4954-4970. ⟨10.1093/nar/gkab245⟩
Nucleic Acids Research, 2021, 49 (9), pp.4954-4970. ⟨10.1093/nar/gkab245⟩
ISSN: 0305-1048
1362-4962
DOI: 10.1093/nar/gkab245⟩
Popis: Long non-coding RNAs have emerged as critical regulators of cell homeostasis by modulating gene expression at chromatin level for instance. Here, we report that the lncRNA ANRIL, associated with several pathologies, binds to thousands of loci dispersed throughout the mammalian genome sharing a 21-bp motif enriched in G/A residues. By combining ANRIL genomic occupancy with transcriptomic analysis, we established a list of 65 and 123 genes potentially directly activated and silenced by ANRIL in trans, respectively. We also found that Exon8 of ANRIL, mainly made of transposable elements, contributes to ANRIL genomic association and consequently to its trans-activity. Furthermore, we showed that Exon8 favors ANRIL’s association with the FIRRE, TPD52L1 and IGFBP3 loci to modulate their expression through H3K27me3 deposition. We also investigated the mechanisms engaged by Exon8 to favor ANRIL’s association with the genome. Our data refine ANRIL’s trans-activity and highlight the functional importance of TEs on ANRIL’s activity.
Databáze: OpenAIRE