CEBPA phase separation links transcriptional activity and 3D chromatin hubs

Christou-Kent, Marie; Cuartero, Sergi; Garcia-Cabau, Carla; Ruehle, Julia; Naderi, Julian; Erber, Julia; Neguembor, Maria Victoria; Plana Carmona, Marcos, 1993-; Alcoverro-Bertran, Marc; Andrés Aguayo, Luisa de; Klonizakis, Antonios; Julià Vilella, Eric; Lynch, Cian J.; Serrano, Manuel; Hnisz, Denes; Salvatella, Xavier; Graf, T. (Thomas); Stik, Grégoire

CEBPA phase separation links transcriptional activity and 3D chromatin hubs

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dc.contributor.author Christou-Kent, Marie
dc.contributor.author Cuartero, Sergi
dc.contributor.author Garcia-Cabau, Carla
dc.contributor.author Ruehle, Julia
dc.contributor.author Naderi, Julian
dc.contributor.author Erber, Julia
dc.contributor.author Neguembor, Maria Victoria
dc.contributor.author Plana Carmona, Marcos, 1993-
dc.contributor.author Alcoverro-Bertran, Marc
dc.contributor.author Andrés Aguayo, Luisa de
dc.contributor.author Klonizakis, Antonios
dc.contributor.author Julià Vilella, Eric
dc.contributor.author Lynch, Cian J.
dc.contributor.author Serrano, Manuel
dc.contributor.author Hnisz, Denes
dc.contributor.author Salvatella, Xavier
dc.contributor.author Graf, T. (Thomas)
dc.contributor.author Stik, Grégoire
dc.date.accessioned 2023-10-27T06:33:30Z
dc.date.available 2023-10-27T06:33:30Z
dc.date.issued 2023
dc.description.abstract Cell identity is orchestrated through an interplay between transcription factor (TF) action and genome architecture. The mechanisms used by TFs to shape three-dimensional (3D) genome organization remain incompletely understood. Here we present evidence that the lineage-instructive TF CEBPA drives extensive chromatin compartment switching and promotes the formation of long-range chromatin hubs during induced B cell-to-macrophage transdifferentiation. Mechanistically, we find that the intrinsically disordered region (IDR) of CEBPA undergoes in vitro phase separation (PS) dependent on aromatic residues. Both overexpressing B cells and native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors, liver cells, and trophectoderm cells reveal nuclear CEBPA foci and long-range 3D chromatin hubs at CEBPA-bound regions. In short, we show that CEBPA can undergo PS through its IDR, which may underlie in vivo foci formation and suggest a potential role of PS in regulating CEBPA function.
dc.description.sponsorship We thank the Graf lab members for helpful discussions, and the CRG Genomics, Flow Cytometry and Advanced Light Microscopy core facilities; M.C.-K. was supported by an EMBO postdoctoral fellowship (ALTF 1057-2019) and PCIN-MSCA-fellowship (Ministerio de Ciencia e Innovación PCI2021-122032-2B). S.C. is supported by a “La Caixa” Junior Leader fellowship, by the Jérôme Lejeune Foundation (JLF#1902) and the Spanish Ministry of Science and Innovation (PID2020-117950RA-I00). G.S. was supported by the “Fundación Científica de la Asociación Española Contra el Cáncer.” M.V.N. was supported by People Program (Marie Curie Actions) FP7/2007–2013 under REA grant 6089 and Juan de la Cierva-Incorporación 2017. C.G.-C. acknowledges a graduate fellowship from MINECO (PRE2018-084684). X.S. acknowledges funding from AGAUR (2017 SGR 324), MINECO (BIO2015-70092-R and PID2019-110198RB-I00), and the European Research Council (CONCERT, contract number 648201). This work was funded by the Max Planck Society and partially supported by grants from the Deutsche Forschungsgemeinschaft (DFG) SPP2202 Priority Program Grant HN 4/1-1 (to D.H.) and by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) Plan Estatal 2015, SAF.2015-68740-P (to T.G.). We acknowledge support by the Spanish Ministry of Science and Innovation, to the EMBL partnership, the Centro de Excelencia Severo Ochoa, the Josep Carreras Foundation, and the CERCA Programme / Generalitat de Catalunya.
dc.format.mimetype application/pdf
dc.identifier.citation Christou-Kent M, Cuartero S, Garcia-Cabau C, Ruehle J, Naderi J, Erber J, Neguembor MV, Plana-Carmona M, Alcoverro-Bertran M, De Andres-Aguayo L, Klonizakis A, Julià-Vilella E, Lynch C, Serrano M, Hnisz D, Salvatella X, Graf T, Stik G. CEBPA phase separation links transcriptional activity and 3D chromatin hubs. Cell Rep. 2023 Aug 29;42(8):112897. DOI: 10.1016/j.celrep.2023.112897
dc.identifier.doi http://dx.doi.org/10.1016/j.celrep.2023.112897
dc.identifier.issn 2211-1247
dc.identifier.uri http://hdl.handle.net/10230/58140
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Rep. 2023 Aug 29;42(8):112897
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/648201
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PCI2021-122032-2B
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-117950RA-I00
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PRE2018-084684
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-70092-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110198RB-I00
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword 3D genome organization
dc.subject.keyword CEBPA
dc.subject.keyword CP: Molecular biology
dc.subject.keyword Chromatin hubs
dc.subject.keyword Compartments
dc.subject.keyword Condensates
dc.subject.keyword Gene regulation
dc.subject.keyword Phase separation
dc.subject.keyword Transcription
dc.subject.keyword Transdifferentiation
dc.title CEBPA phase separation links transcriptional activity and 3D chromatin hubs
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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