Structural basis of the DEK-nucleosome complex and its functional implications

The nuclear factor Dek is notably enriched within chromatin; nevertheless, the precise binding mechanism of Dek to the nucleosome remains elusive. In this study, we employ cryo-electron microscopy (cryo-EM) to elucidate the high-resolution structure of the Dek-Nucleosome Core Particle (NCP) complex. We identify specific domains responsible for DEK interaction with the histone octamer and DNA within the nucleosome. The veracity of these binding domains is confirmed through a series of meticulous biochemical experiments. Subsequently, cellular experiments reveal that Dek lacking nucleosome-binding capacity exhibits a deficiency in chromatin interaction. Remarkably, this impairment induces a shift towards the primitive endoderm fate in mouse embryonic stem cells, underscoring the pivotal role of Dek in determining cell fate through its nucleosomal interactions. HA-labeled wild-type DEK and various key domain mutations were overexpressed in DEK-knockout cells. CUT&Tag for HA was employed to assess the impact of mutations on the distribution of Dek on chromatin, while RNA-seq was used to identify transcriptomic changes induced by these mutations in the cells.