Polycomb factor PHF19 controls cell growth and differentiation toward erythroid pathway in chronic myeloid leukemia cells
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- dc.contributor.author García Montolío, Marc, 1991-
- dc.contributor.author Ballaré, Cecilia Julia
- dc.contributor.author Blanco, Enrique
- dc.contributor.author Gutiérrez, Arantxa
- dc.contributor.author Aranda Aragón, Sergio
- dc.contributor.author Gómez, Antonio
- dc.contributor.author Kok, Chung H.
- dc.contributor.author Yeung, David T.
- dc.contributor.author Hughes, Timothy P.
- dc.contributor.author Vizán, Pedro
- dc.contributor.author Di Croce, Luciano
- dc.date.accessioned 2021-07-23T06:57:28Z
- dc.date.available 2021-07-23T06:57:28Z
- dc.date.issued 2021
- dc.description.abstract Polycomb group (PcG) of proteins are a group of highly conserved epigenetic regulators involved in many biological functions, such as embryonic development, cell proliferation, and adult stem cell determination. PHD finger protein 19 (PHF19) is an associated factor of Polycomb repressor complex 2 (PRC2), often upregulated in human cancers. In particular, myeloid leukemia cell lines show increased levels of PHF19, yet little is known about its function. Here, we have characterized the role of PHF19 in myeloid leukemia cells. We demonstrated that PHF19 depletion decreases cell proliferation and promotes chronic myeloid leukemia (CML) differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through a direct regulation of the cell cycle inhibitor p21. Furthermore, we observed that MTF2, a PHF19 homolog, partially compensates for PHF19 depletion in a subset of target genes, instructing specific erythroid differentiation. Taken together, our results show that PHF19 is a key transcriptional regulator for cell fate determination and could be a potential therapeutic target for myeloid leukemia treatment.
- dc.description.sponsorship This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU2016-75008-P and PID2019-108322GB-100), “Fundación Vencer El Cancer” (VEC), the European Regional Development Fund (FEDER), and from AGAUR (SGR 2017-2019). SA was funded by the Ramon y Cajal program of the Ministerio de Ciencia, Innovación y Universidades, the European Social Fund under the reference number RYC-2018-025002-I, and the Instituto de Salud Carlos III-FEDER (PI19/01814)
- dc.format.mimetype application/pdf
- dc.identifier.citation García-Montolio M, Ballaré C, Blanco E, Gutiérrez A, Aranda S, Gómez A et al. Polycomb factor PHF19 controls cell growth and differentiation toward erythroid pathway in chronic myeloid leukemia cells. Front Cell Dev Biol. 2021 Apr 29;9:655201. DOI: 10.3389/fcell.2021.655201
- dc.identifier.doi http://dx.doi.org/10.3389/fcell.2021.655201
- dc.identifier.issn 2296-634X
- dc.identifier.uri http://hdl.handle.net/10230/48285
- dc.language.iso eng
- dc.publisher Frontiers Media
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2016-75008-P
- dc.rights © 2021 Marc García-Montolio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by/4.0/
- dc.subject.other Leucèmia
- dc.subject.other Genètica
- dc.title Polycomb factor PHF19 controls cell growth and differentiation toward erythroid pathway in chronic myeloid leukemia cells
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion