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CEBPA phase separation links transcriptional activity and 3D chromatin hubs

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. A large intrinsically disordered region (IDR) enables CEBPA to undergo in vitro phase separation and to co-condense with transcriptional partners, which is at least partially mediated by aromatic residues. Furthermore, CEBPA forms visible nuclear condensates in transdifferentiating B cells that co-localize with co-activator condensates and recover rapidly upon photobleaching. Finally, native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors (GMPs), liver cells and trophectoderm cells also reveal nuclear CEBPA condensates and long-range 3D chromatin hubs at CEBPA-bound regions. These findings support a model in which CEBPA acts as a 3D genome structural organizer and suggest that this effect is mediated at least in part by its phase-separation capacity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221167 | GEO | 2023/07/24

REPOSITORIES: GEO

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