CEBPA phase separation links transcriptional activity and 3D chromatin hubs

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 ex...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/58140
Acceso en línea:http://hdl.handle.net/10230/58140
http://dx.doi.org/10.1016/j.celrep.2023.112897
Access Level:acceso abierto
Palabra clave:3D genome organization
CEBPA
CP: Molecular biology
Chromatin hubs
Compartments
Condensates
Gene regulation
Phase separation
Transcription
Transdifferentiation
Descripción
Sumario: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.

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