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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Bibliographic Details
Authors: Christou-Kent, Marie, Cuartero, Sergi|||0000-0002-9338-583X, Garcia-Cabau, Carla|||0000-0003-0533-0642, Ruehle, Julia, Naderi, Julian, Erber, Julia, Neguembor, Maria Victoria, Plana-Carmona, Marcos, Alcoverro Bertran, Marc, de Andrés-Aguayo, Luisa|||0000-0001-6717-242X, Klonizakis, Antonios, Julià Vilella, Eric, Lynch, Cian, Serrano, Manuel|||0000-0001-7177-9312, Hnisz, Denes|||0000-0002-6256-1693, Salvatella, Xavier|||0000-0002-8371-4185, Graf, Thomas|||0000-0003-2774-4117, Stik, Grégoire|||0000-0002-1404-1992
Format: article
Publication Date:2023
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:289527
Online Access:https://ddd.uab.cat/record/289527
https://dx.doi.org/urn:doi:10.1016/j.celrep.2023.112897
Access Level:Open access
Keyword:CEBPA
Condensates
Phase separation
Transcription
Chromatin hubs
Transdifferentiation
Gene regulation
3D genome organization
Compartments
Description
Summary: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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