TFIIIC binding to alu elements controls gene expression via chromatin looping and histone acetylation

Ferrari, Roberto; De Llobet, Lara Isabel; Di Vona, Chiara, 1981-; Le Dily, François; Vidal Ocabo, Enrique; Lloutas, Antonios; Quilez Oliete, Javier; Jochem, Laura; Cuts, Erin; Dieci, Giorgio; Vannini, Alessandro; Teichmann, Martin; de la Luna, Susana; Beato, Miguel

TFIIIC binding to alu elements controls gene expression via chromatin looping and histone acetylation

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dc.contributor.author Ferrari, Roberto
dc.contributor.author De Llobet, Lara Isabel
dc.contributor.author Di Vona, Chiara, 1981-
dc.contributor.author Le Dily, François
dc.contributor.author Vidal Ocabo, Enrique
dc.contributor.author Lloutas, Antonios
dc.contributor.author Quilez Oliete, Javier
dc.contributor.author Jochem, Laura
dc.contributor.author Cuts, Erin
dc.contributor.author Dieci, Giorgio
dc.contributor.author Vannini, Alessandro
dc.contributor.author Teichmann, Martin
dc.contributor.author de la Luna, Susana
dc.contributor.author Beato, Miguel
dc.date.accessioned 2020-04-17T07:01:05Z
dc.date.available 2020-04-17T07:01:05Z
dc.date.issued 2020
dc.description.abstract How repetitive elements, epigenetic modifications, and architectural proteins interact ensuring proper genome expression remains poorly understood. Here, we report regulatory mechanisms unveiling a central role of Alu elements (AEs) and RNA polymerase III transcription factor C (TFIIIC) in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of AEs pre-marked by the activity-dependent neuroprotector homeobox Protein (ADNP) and located near cell-cycle genes recruits TFIIIC, which alters their chromatin accessibility by direct acetylation of histone H3 lysine-18 (H3K18). This facilitates the contacts of AEs with distant CTCF sites near promoter of other cell-cycle genes, which also become hyperacetylated at H3K18. These changes ensure basal transcription of cell-cycle genes and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor regulates 3D genome folding and expression.
dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness Centro de Excelencia Severo Ochoa 2013–2017 SEV-2012-0208 (to CRG) and BFU2016-76141-P (to S.d.l.L.); ACER (to CRG); Italian Association for Cancer Research (AIRC, grant IG16877 to G.D.); the Cancer Research UK Programme Foundation (CR-UK C47547/A21536 to A.V.); a Wellcome Trust Investigator Award (200818/Z/16/Z to A.V.); and the European Research Council (ERC) under the European Union’s Seventh Framework Programme (FP7/2007–2013/ERC Synergy grant agreement 609989-4DGenome to M.B.). We acknowledge the support of the Spanish Ministry of Science, Innovation, and Universities to the EMBL partnership, the CERCA Programme/Generalitat de Catalunya , and the Centro de Excelencia Severo Ochoa. The ERC provided funding for the open access charge. The proteomics analyses were performed at the CRG/UPF Proteomics Unit (part of the of Proteored, PRB3; supported by grant PT17/0019 [ISCIII and ERDF]). This work was also supported by the Ligue Contre le Cancer (to M.T.)
dc.format.mimetype application/pdf
dc.identifier.citation Ferrari R, de Llobet Cucalon LI, Di Vona C, Le Dilly F, Vidal E, Lioutas A et al. TFIIIC binding to alu elements controls gene expression via chromatin looping and histone acetylation. Mol Cell. 2020 Feb 6; 77(3): 475-487.e11. DOI: 10.1016/j.molcel.2019.10.020
dc.identifier.doi http://dx.doi.org/10.1016/j.molcel.2019.10.020
dc.identifier.issn 1097-2765
dc.identifier.uri http://hdl.handle.net/10230/44261
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Molecular Cell. 2020 Feb 6; 77(3): 475-87.e11
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-76141-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.other Expressió gènica
dc.subject.other Cromatina
dc.subject.other Histones
dc.title TFIIIC binding to alu elements controls gene expression via chromatin looping and histone acetylation
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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