2016
Henry, Ryan A; Mancuso, Pietro; Kuo, Yin-Ming; Tricarico, Rossella; Tini, Marc; Cole, Philip A; Bellacosa, Alfonso; Andrews, Andrew J
Interaction with the DNA Repair Protein Thymine DNA Glycosylase Regulates Histone Acetylation by p300 Journal Article
In: Biochemistry, vol. 55, no. 49, pp. 6766-6775, 2016, ISSN: 1520-4995.
Abstract | Links | BibTeX | Tags: Acetylation, Animals, Cell Line, Cells, Cultured, DNA Repair, E1A-Associated p300 Protein, Histones, Knockout, Mice, Thymine DNA Glycosylase
@article{1299948,
title = {Interaction with the DNA Repair Protein Thymine DNA Glycosylase Regulates Histone Acetylation by p300},
author = {Ryan A Henry and Pietro Mancuso and Yin-Ming Kuo and Rossella Tricarico and Marc Tini and Philip A Cole and Alfonso Bellacosa and Andrew J Andrews},
doi = {10.1021/acs.biochem.6b00841},
issn = {1520-4995},
year = {2016},
date = {2016-12-01},
journal = {Biochemistry},
volume = {55},
number = {49},
pages = {6766-6775},
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.},
keywords = {Acetylation, Animals, Cell Line, Cells, Cultured, DNA Repair, E1A-Associated p300 Protein, Histones, Knockout, Mice, Thymine DNA Glycosylase},
pubstate = {published},
tppubtype = {article}
}
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.