C/EBPalpha activates pre-existing and de novo macrophage enhancers during induced pre-B cell transdifferentiation and myelopoiesis

van Oevelen, Chris; Collombet, Samuel; Vicent, Guillermo Pablo; Hoogenkamp, Maarten; Lepoivre, Cyrille; Badeaux, Aimee; Bussmann, Lars; Sardina, Jose Luis; Thieffry, Denis; Beato, Miguel; Shi, Yang; Bonifer, Constanze; Graf, T. (Thomas)

C/EBPalpha activates pre-existing and de novo macrophage enhancers during induced pre-B cell transdifferentiation and myelopoiesis

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dc.contributor.author van Oevelen, Chrisca
dc.contributor.author Collombet, Samuelca
dc.contributor.author Vicent, Guillermo Pabloca
dc.contributor.author Hoogenkamp, Maartenca
dc.contributor.author Lepoivre, Cyrilleca
dc.contributor.author Badeaux, Aimeeca
dc.contributor.author Bussmann, Larsca
dc.contributor.author Sardina, Jose Luisca
dc.contributor.author Thieffry, Denisca
dc.contributor.author Beato, Miguelca
dc.contributor.author Shi, Yangca
dc.contributor.author Bonifer, Constanzeca
dc.contributor.author Graf, T. (Thomas)ca
dc.date.accessioned 2015-11-23T13:49:25Z
dc.date.available 2015-11-23T13:49:25Z
dc.date.issued 2015
dc.description.abstract Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells.ca
dc.description.sponsorship This work was supported by the Ministerio de Educacion y Ciencia, SAF.2012- 37167, AGAUR 2009 SGR768, EU-FP7 project BLUEPRINT (282510), and Fundacio la Marato TV3. C.B. was funded by a program grant (LLR 7001) from Leukemia Lymphoma Research UK.en
dc.format.mimetype application/pdfca
dc.identifier.citation van Oevelen C, Collombet S, Vicent G, Hoogenkamp M, Lepoivre C, Badeaux A et al. C/EBPalpha activates pre-existing and de novo macrophage enhancers during induced pre-B cell transdifferentiation and myelopoiesis. Stem cell reports. 2015;5(2):232-47. DOI: 10.1016/j.stemcr.2015.06.007ca
dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2015.06.007
dc.identifier.issn 2213-6711
dc.identifier.uri http://hdl.handle.net/10230/25184
dc.language.iso engca
dc.publisher Elsevierca
dc.relation.ispartof Stem cell reports. 2015;5(2):232-47
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-37167
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0ca
dc.subject.other Cèl·lules B
dc.subject.other Cèl·lules mare embrionàries
dc.title C/EBPalpha activates pre-existing and de novo macrophage enhancers during induced pre-B cell transdifferentiation and myelopoiesisca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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