Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex

Panatta, Emanuele; Lena, Anna Maria; Mancini, Mara; Smirnov, Artem; Marini, Alberto; Delli Ponti, Riccardo, 1987-; Botta Orfila, Teresa; Tartaglia, Gian Gaetano; Mauriello, Alessandro; Zhang, Xinna; Calin, George A.; Melino, Gerry; Candi, Eleonora

Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex

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dc.contributor.author Panatta, Emanuele
dc.contributor.author Lena, Anna Maria
dc.contributor.author Mancini, Mara
dc.contributor.author Smirnov, Artem
dc.contributor.author Marini, Alberto
dc.contributor.author Delli Ponti, Riccardo, 1987-
dc.contributor.author Botta Orfila, Teresa
dc.contributor.author Tartaglia, Gian Gaetano
dc.contributor.author Mauriello, Alessandro
dc.contributor.author Zhang, Xinna
dc.contributor.author Calin, George A.
dc.contributor.author Melino, Gerry
dc.contributor.author Candi, Eleonora
dc.date.accessioned 2020-03-19T10:08:11Z
dc.date.available 2020-03-19T10:08:11Z
dc.date.issued 2020
dc.description.abstract The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.
dc.description.sponsorship This work has been mainly supported by Italian Ministry of Health and IDI‐IRCCS (RC to EC) and by AIRC IG grant 22206 to EC. This work has also been partially supported by the European Research Council (RIBOMYLOME_309545), the Spanish Ministry of Economy and Competitiveness (BFU2014‐55054‐P) and “Fundació La Marató de TV3” (PI043296)
dc.format.mimetype application/pdf
dc.identifier.citation Panatta E, Lena AM, Mancini M, Smirnov A, Marini A, Delli Ponti R. Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex. EMBO Rep. 2020 Mar 4; 21(3): e46734. DOI: 10.15252/embr.201846734
dc.identifier.doi http://dx.doi.org/10.15252/embr.201846734
dc.identifier.issn 1469-221X
dc.identifier.uri http://hdl.handle.net/10230/43950
dc.language.iso eng
dc.publisher EMBO Press
dc.relation.ispartof EMBO Reports. 2020 Mar 4; 21(3): e46734
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/309545
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014‐55054‐P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Epidermis
dc.subject.other Queratinòcit
dc.subject.other Gens
dc.title Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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