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Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity. | LitMetric

AI Article Synopsis

  • p300 is a key protein that helps with important cell functions like differentiation and growth, and it forms distinct clusters in the nucleus through a process called phase separation.
  • This phase separation is influenced by p300's ability to modify itself chemically and depends on specific parts of its structure, including a region that inhibits its activity and its acetyltransferase domain.
  • The p300 clusters hold onto chromatin elements and are associated with regions of DNA that are less active, which suggests that p300 might function as a reservoir of proteins with reduced activity, strategically positioning itself at regions of chromatin that are either ready to be activated or kept repressed.

Article Abstract

The transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322156PMC
http://dx.doi.org/10.1038/s41467-021-24950-8DOI Listing

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