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

Yi Zhang, Kyle Brown, Yucong Yu, Ziad Ibrahim, Mohamad Zandian, Hongwen Xuan, Steven Ingersoll, Thomas Lee, Christopher C. Ebmeier, Jiuyang Liu, Daniel Panne, Xiaobing Shi, Xiaojun Ren and Tatiana G. Kutateladze ()
Additional contact information
Yi Zhang: University of Colorado School of Medicine
Kyle Brown: University of Colorado
Yucong Yu: Van Andel Research Institute
Ziad Ibrahim: University of Leicester
Mohamad Zandian: University of Colorado School of Medicine
Hongwen Xuan: Van Andel Research Institute
Steven Ingersoll: University of Colorado
Thomas Lee: University of Colorado
Christopher C. Ebmeier: University of Colorado
Jiuyang Liu: University of Colorado School of Medicine
Daniel Panne: University of Leicester
Xiaobing Shi: Van Andel Research Institute
Xiaojun Ren: University of Colorado
Tatiana G. Kutateladze: University of Colorado School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24950-8

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DOI: 10.1038/s41467-021-24950-8

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