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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Detalhes 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 documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/58140
Acesso em linha:http://hdl.handle.net/10230/58140
http://dx.doi.org/10.1016/j.celrep.2023.112897
Access Level:Acceso aberto
Palavra-chave:3D genome organization
CEBPA
CP: Molecular biology
Chromatin hubs
Compartments
Condensates
Gene regulation
Phase separation
Transcription
Transdifferentiation
Descrição
Resumo: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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