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Garcia-Cabau CAuthorLynch CAuthorSerrano MAuthorSalvatella XAuthor

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August 29, 2023
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Article

CEBPA phase separation links transcriptional activity and 3D chromatin hubs

Publicated to: Cell Reports. 42 (8): 112897- - 2023-08-29 42(8), DOI: 10.1016/j.celrep.2023.112897

Authors: 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

Affiliations

Altos Labs, Cambridge Institute of Science, Cambridge CB21 6GP, UK. - Author
Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain - Author
Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Baldiri Reixac 10, Barcelona 08028, Spain - Author
Cambridge Inst Sci, Altos Labs, Cambridge CB21 6GP, England - Author
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain - Author
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain. - Author
Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany. - Author
Germans Trias I Pujol Res Inst IGTP, Badalona, Spain - Author
Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain. - Author
ICREA, Passeig Lluis Co 23, Barcelona 08010, Spain - Author
ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain. - Author
Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain - Author
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain. - Author
Josep Carreras Leukaemia Res Inst IJC, Badalona, Spain - Author
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain - Author
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain. - Author
Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain. Electronic address: gstik@carrerasresearch.org. - Author
Max Planck Inst Mol Genet, Dept Genome Regulat, Ihnestr 63-73, D-14195 Berlin, Germany - Author
Univ Pompeu Fabra UPF, Barcelona, Spain - Author
Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: thomas.graf@crg.eu. - Author
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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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

colocalizationconformationdomainsgene-regulationgenomemaintenanceprinciplesrevealstransdifferentiation3d genome organizationC/ebp-alphaCebpaChromatin hubsCompartmentsCondensatesCp: molecular biologyGene regulationPhase separationTranscriptionTransdifferentiation

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cell Reports due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 36/205, thus managing to position itself as a Q1 (Primer Cuartil), in the category Cell Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.54. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-12-17, the following number of citations:

  • WoS: 13
  • Europe PMC: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-17:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 37.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 39 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.
  • The number of mentions on the social network X (formerly Twitter): 15 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany; United Kingdom.

Awards linked to the item

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 Innovacion PCI2021-122032-2B) . S.C. is supported by a "La Caixa"Junior Leader fellowship, by the Jerome Lejeune Foundation (JLF#1902) and the Spanish Ministry of Science and Innovation (PID2020-117950RA-I00) . G.S. was supported by the "Fundacion Cientifica de la Asociacion Espanola Contra el Cancer."M.V.N. was supported by People Program (Marie Curie Actions) FP7/2007- 2013 under REA grant 6089 and Juan de la Cierva-Incorporacion 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 partner-ship, the Centro de Excelencia Severo Ochoa, the Josep Carreras Foundation, and the CERCA Programme/Generalitat de Catalunya.