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Interaction with the DNA Repair Protein Thymine DNA Glycosylase Regulates Histone Acetylation by p300
Biochemistry. 2016 Dec 13;55(49) :6766-6775
PMID: 27951654    PMCID: PMC5206798    URL: https://www.ncbi.nlm.nih.gov/pubmed/27951654
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Abstract
How protein-protein interactions regulate and alter histone modifications is a major unanswered question in epigenetics. The histone acetyltransferase p300 binds thymine DNA glycosylase (TDG); utilizing mass spectrometry to measure site-specific changes in histone acetylation, we found that the absence of TDG in mouse embryonic fibroblasts leads to a reduction in the rate of histone acetylation. We demonstrate that TDG interacts with the CH3 domain of p300 to allosterically promote p300 activity to specific lysines on histone H3 (K18 and K23). However, when TDG concentrations approach those of histones, TDG acts as a competitive inhibitor of p300 histone acetylation. These results suggest a mechanism for how histone acetylation is fine-tuned via interaction with other proteins, while also highlighting a connection between regulators of two important biological processes: histone acetylation and DNA repair/demethylation.
Notes
1520-4995 Henry, Ryan A Mancuso, Pietro Kuo, Yin-Ming Tricarico, Rossella Tini, Marc Cole, Philip A Bellacosa, Alfonso Andrews, Andrew J R01 GM062437/GM/NIGMS NIH HHS/United States R37 GM062437/GM/NIGMS NIH HHS/United States Journal Article United States Biochemistry. 2016 Dec 13;55(49):6766-6775. Epub 2016 Dec 1.