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Henry RA , Kuo YM , Bhattacharjee V , Yen TJ , Andrews AJ
Changing the Selectivity of p300 by Acetyl-CoA Modulation of Histone Acetylation
Acs Chemical Biology. 2015 Jan;10(1) :146-156
PMID: 25325435 PMCID: PMC4327817 URL: https://www.ncbi.nlm.nih.gov/pubmed/25325435
AbstractDetermining how histone acetylation is regulated is vital for treating the many diseases associated with its misregulation, including heart disease, neurological disorders, and cancer. We have previously reported that acetyl-CoA levels alter p300 histone acetylation in a site-specific manner in vitro. Here, we further investigate how changing acetyl-CoA concentrations alter the histone acetylation pattern by altering p300 specificity. Interestingly, these changes are not a simple global change in acetylation, but rather site specific changes, whereby acetylation at some sites increase while others decrease. We also demonstrate how the p300 inhibitor C646 can pharmacologically alter p300 histone acetylation patterns in vitro and in cells. This study provides insight into the mechanisms regulating p300 residue specificity, a potential means for altering p300 dependent histone acetylation, and an investigation into altering histone acetylation patterns in cells.
NotesHenry, Ryan A. Kuo, Yin-Ming Bhattacharjee, Vikram Yen, Timothy J. Andrews, Andrew J.