The PHD finger of p300 influences its ability to acetylate histone and non-histone targets.

Abstract

In enzymes that regulate chromatin structure, the combinatorial occurrence of modules that alter and recognise histone modifications is a recurrent feature. In this study, we explored the functional relationship between the acetyltransferase domain and the adjacent bromodomain/PHD finger (bromo/PHD) region of the transcriptional coactivator p300. We found that the bromo/PHD region of p300 can bind to the acetylated catalytic domain in vitro and augment the catalytic activity of the enzyme. Deletion of the PHD finger, but not the bromodomain, impaired the ability of the enzyme to acetylate histones in vivo, whilst it enhanced p300 self-acetylation. A point mutation in the p300 PHD finger that is related to the Rubinstein-Taybi syndrome resulted in increased self-acetylation but retained the ability to acetylate histones. Hence, the PHD finger appears to negatively regulate self-acetylation. Furthermore, our data suggest that the PHD finger has a role in the recruitment of p300 to chromatin.

• Authors: Johannes G M Rack, Timo Lutter, Gro Elin Kjæreng Bjerga, Corina Guder, Christine Ehrhardt, Signe Värv, Mathias Ziegler, Rein Aasland
• Journal: Journal of molecular biology (J Mol Biol) Vol. 426 Issue 24 Pg. 3960-3972 (Dec 12 2014) ISSN: 1089-8638 [Electronic] Netherlands
• PMID: 25158095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Histones
• E1A-Associated p300 Protein
• EP300 protein, human

Topics

• Acetylation
• Binding Sites (genetics)
• Biocatalysis
• E1A-Associated p300 Protein (chemistry, genetics, metabolism)
• HEK293 Cells
• HeLa Cells
• Histones (metabolism)
• Humans
• Immunoblotting
• Immunohistochemistry
• Microscopy, Fluorescence
• Models, Molecular
• Point Mutation
• Protein Binding
• Protein Structure, Tertiary