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DNA methylation editing by CRISPR-guided excision of 5-methylcytosine
dc.contributor.author | Devesa-Guerra, I. | |
dc.contributor.author | Morales-Ruiz, T. | |
dc.contributor.author | Pérez Roldán, Juan | |
dc.contributor.author | Parrilla-Doblas, Jara | |
dc.contributor.author | Dorado León, Macarena | |
dc.contributor.author | García-Ortiz, M.V. | |
dc.contributor.author | Ariza, Rafael R. | |
dc.contributor.author | Roldán-Arjona, Teresa | |
dc.date.accessioned | 2020-02-24T17:45:58Z | |
dc.date.available | 2020-02-24T17:45:58Z | |
dc.date.issued | 2020 | |
dc.identifier.uri | http://hdl.handle.net/10396/19631 | |
dc.description.abstract | Tools for active targeted DNA demethylation are required to increase our knowledge about regulation and specific functions of this important epigenetic modification. DNA demethylation in mammals involve TET-mediated oxidation of 5- methylcytosine (5-meC), which may promote its replication-dependent dilution and/or active removal through base excision repair (BER). However, it is still unclear whether oxidized derivatives of 5-meC are simply DNA demethylation intermediates or rather epigenetic marks on their own. Unlike animals, plants have evolved enzymes that directly excise 5-meC without previous modification. In this work we have fused the catalytic domain of Arabidopsis ROS1 5-meC DNA glycosylase to a CRISPRassociated null-nuclease (dCas9) and analyzed its capacity for targeted reactivation of methylation-silenced genes, in comparison to other dCas9-effectors. We found that dCas9-ROS1, but not dCas9-TET1, is able to reactivate methylation-silenced genes and induce partial demethylation in a replication-independent manner. We also found that reactivation induced by dCas9-ROS1, as well as that achieved by two different CRISPR-based chromatin effectors (dCas9-VP160 and dCas9-p300), generally decreases with methylation density. Our results suggest that plant 5-meC DNA glycosylases are a valuable addition to the CRISPR-based toolbox for epigenetic editing. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/4.0/ | es_ES |
dc.source | Journal of Molecular Biology 432, 2204-2216 (2020) | es_ES |
dc.subject | Epigenetics | es_ES |
dc.subject | DNA demethylation | es_ES |
dc.subject | DNA glycosylases | es_ES |
dc.subject | TET dioxygenases | es_ES |
dc.title | DNA methylation editing by CRISPR-guided excision of 5-methylcytosine | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.jmb.2020.02.007 | es_ES |
dc.relation.projectID | Gobierno de España. BFU2016-80728-P | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |