CEBPA phase separation links transcriptional activity and 3D chromatin hubs

• DOI: 10.1016/j.celrep.2023.112897
• Publication Date: 2023-07-29T15:46:02Z
• Authors: Marie Christou-Kent; Sergi Cuartero; Carla Garcia-Cabau; Julia Ruehle; Julian Naderi; Julia Erber; Maria Victoria Ne...; Marcos Plana-Carmona; Marc Alcoverro-Be...; Luisa De Andres-A...; Antonios Klonizakis; Eric Julià-Vilella; Cian Lynch; Manuel Serrano; Denes Hnisz; Xavier Salvatella; Thomas Graf; Grégoire Stik
• Keywords: CEBPA; Transdifferentiation

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) organization remain incompletely understood. Here we present evidence that the lineage-instructive TF CEBPA drives extensive chromatin compartment switching promotes formation of long-range hubs during induced B cell-to-macrophage transdifferentiation. Mechanistically, find intrinsically disordered region (IDR) undergoes in vitro phase separation (PS) dependent on aromatic residues. Both overexpressing cells native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors, liver cells, trophectoderm reveal nuclear foci 3D at CEBPA-bound regions. In short, show can undergo PS its IDR, which may underlie vivo suggest a potential role regulating function.