HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies.
Cell Rep
; 34(3): 108638, 2021 01 19.
Article
in En
| MEDLINE
| ID: mdl-33472068
ABSTRACT
Histone acetylation levels are regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) that antagonistically control the overall balance of this post-translational modification. HDAC inhibitors (HDACi) are potent agents that disrupt this balance and are used clinically to treat diseases including cancer. Despite their use, little is known about their effects on chromatin regulators, particularly those that signal through lysine acetylation. We apply quantitative genomic and proteomic approaches to demonstrate that HDACi robustly increases a low-abundance histone 4 polyacetylation state, which serves as a preferred binding substrate for several bromodomain-containing proteins, including BRD4. Increased H4 polyacetylation occurs in transcribed genes and correlates with the targeting of BRD4. Collectively, these results suggest that HDAC inhibition functions, at least in part, through expansion of a rare histone acetylation state, which then retargets lysine-acetyl readers associated with changes in gene expression, partially mimicking the effect of bromodomain inhibition.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Histones
/
Cell Cycle Proteins
/
Histone Deacetylase Inhibitors
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2021
Document type:
Article
Affiliation country:
United States