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Study of three-dimensional structure of chromatin through a 4C-seq experiment in mouse NSC shControl and shJMJD3 upon TGFβ treatment [Chst8]

ABSTRACT: In this study we analyzed how multiple enhancers arrange in the 3D-space to control the activation of a specific promoter. Specifically, we did a 4C-seq experiment on a ~374 Kb locus where enhancers abound, which revealed that the TGFβ pathway drives the establishment of contacts between cis-regulatory elements that facilitates the assembly of an enhancer-cluster and precise gene activation. We discovered that the TGFβ pathway coactivator JMJD3 is essential to maintain these 3D-structures, as when it is depleted the contacts are lost but they are restablished when re-expressing the protein. To do that, JMJD3 requires a proline-rich intrinsically disordered region, which is essential for proper gene activation due to its involvement in the formation of phase-separated biomolecular condensates. Overall, we uncover novel functions for the ubiquitous coactivator JMJD3, and we shed light on the relationships between the 3D-conformation of the chromatin, and their role in regulating the TGFβ-driven response during mammalian neurogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE197010 | GEO | 2022/04/21

REPOSITORIES: GEO

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