Polycomb regulates mesoderm cell fate-specification in embryonic stem cells through activation and repression mechanisms
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- dc.contributor.author Morey Ramonell, Lluísca
- dc.contributor.author Santanach Buxaderas, Alexandra, 1988-ca
- dc.contributor.author Blanco, Enriqueca
- dc.contributor.author Aloia, Luigica
- dc.contributor.author Nora, Elphège P.ca
- dc.contributor.author Bruneau, Benoit G.ca
- dc.contributor.author Di Croce, Lucianoca
- dc.date.accessioned 2016-07-21T17:28:37Z
- dc.date.available 2016-09-03T02:00:03Z
- dc.date.issued 2015
- dc.description.abstract Polycomb complexes (PRC1 and PRC2) are essential regulators of epigenetic gene silencing in embryonic and adult stem cells. Emerging evidence suggests that the core subunit composition regulates distinct biological processes, yet little is known about the mechanistic underpinnings of how differently composed Polycomb complexes instruct and maintain cell fate. Here we find that Mel18, also known as Pcgf2 and one of six Pcgf paralogs, uniquely regulates PRC1 to specify mesoderm cell fate in embryonic stem cells. Mechanistically, Mel18 functions as a classical Polycomb protein during early cardiac mesoderm differentiation by repressing pluripotency, lineage specification, late cardiac differentiation, and negative regulators of the BMP pathway. However, Mel18 also positively regulates expression of key mesoderm transcription factors, revealing an unexpected function of Mel18 in gene activation during cardiac differentiation. Taken together, our findings reveal that Mel18 is required to specify PRC1 function in both a context- and stage-specific manner.ca
- dc.description.sponsorship This work was supported by grants from the Spanish “Ministerio de Educación y Ciencia” (SAF2013-48926-P), from AGAUR, from Fundació “La Marató de TV3”, and from the European Commission’s 7th Framework Program 4DCellFate (277899)
- dc.format.mimetype application/pdfca
- dc.identifier.citation Morey L, Santanach A, Blanco E, Aloia L, Nora EP, Bruneau BG et al. Polycomb regulates mesoderm cell fate-specification in embryonic stem cells through activation and repression mechanisms. Cell stem cell. 2015;17(3):300-15. DOI: 10.1016/j.stem.2015.08.009ca
- dc.identifier.doi http://dx.doi.org/10.1016/j.stem.2015.08.009
- dc.identifier.issn 1934-5909
- dc.identifier.uri http://hdl.handle.net/10230/27101
- dc.language.iso engca
- dc.publisher Elsevierca
- dc.relation.ispartof Cell stem cell. 2015;17(3):300-15
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2013-48926-P
- dc.rights © Elsevier http://dx.doi.org/10.1016/j.stem.2015.08.009ca
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Diferenciació cel·lularca
- dc.subject.other Regulació genèticaca
- dc.title Polycomb regulates mesoderm cell fate-specification in embryonic stem cells through activation and repression mechanismsca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/acceptedVersionca