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Nucleosomes gate cofactor access to the transcription factor p53 [ChIP-seq]

GSE299056 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2025/06/15 Platform GPL19057
Summary
The transcription factor p53 regulates cell cycle progression, apoptosis, and the DNA damage response. A large fraction of p53 resides in inaccessible chromatin, where it is unclear how nucleosomes impact p53’s ability to engage cofactors. We examined the interaction of p53 with the members of the ubiquitin proteasome system (UPS) on chromatin. At two distinct motif locations (SHL-5.7, +5.9), the viral E3 ubiquitin ligase E6-E6AP was unable to bind nucleosome-engaged p53. The deubiquitinase USP7, on the other hand, readily engages nucleosome-bound p53 in vitro and in cells. The corresponding cryo-EM structure finds USP7 intricately engaged with p53 and nucleosomes, with the TRAF domain contacting the nucleosome at SHL-5.7 sandwiched between the p53 tetramerisation and DNA-binding domains. The structures of p53 bound to USP7/nucleosomes and E6AP illustrate how chromatin imposes a barrier for some, albeit not all p53 interactors. Our work suggests a conceptual framework for how nucleosomes govern TF/cofactor interactions.
Published in
Nucleosomes specify co-factor access to p53
Chakraborty D, Sandate CR, Isbel L et al. · Molecular cell 2025 · PMID 40713947 · doi:10.1016/j.molcel.2025.06.027
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Also filed as BioProject PRJNA1272473 and SRA study SRP590104. Searching any of these in the dataset finder brings you back here.

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