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| Status |
Public on Oct 20, 2020 |
| Title |
HDAC inhibitors result in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Histone acetylation is associated with active transcription and serves as a binding site for reader proteins that function in transcriptional initiation and elongation. Histone acetylation levels are regulated through the actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs) that antagonistically control the overall balance of this posttranslational modification. HDAC inhibitors (HDACi) are potent agents that disrupt this balance and are used clinically to treat a range of human diseases including cancer. Despite their clinical applications, little is known about their chromatin effects. By applying quantitative genomic and proteomic approaches, we demonstrate that HDACi robustly increase a low abundance histone acetylation state (H4 K5ac/K8ac/12ac/K16ac), which serves as a preferred binding substrate for a variety of human bromodomain-containing proteins, including BRD4. This H4 polyacetylation signature observed after HDACi treatment accumulates in the transcribed regions of genes and correlates with the targeting of BRD4 to genes with increased gene expression. Collectively, these results suggest that HDAC inhibition functions, at least in part, through expansion of a rare chromatin acetylation state, which then retargets lysine-acetyl reader proteins associated with changes in gene expression.
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| Overall design |
Examination of H4ac and BRD4 in HL60 cells before and after SAHA treatment
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| Contributor(s) |
Slaughter MJ, Shanle EK, Khan A, Chua KF, Hong T, Boxer LD, Allis CD, Josefowicz SZ, Garcia BA, Rothbart SB, Strahl BD, Davis IJ |
| Citation(s) |
33472068 |
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| Submission date |
Oct 19, 2020 |
| Last update date |
Feb 22, 2021 |
| Contact name |
Austin J Hepperla |
| E-mail(s) |
hepperla@unc.edu
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| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Genetics
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| Street address |
7018B Mary Ellen Jones Building
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA669844 |
| SRA |
SRP287655 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE159620_HL60_H4ac_DMSO.vs.SAHA_spikeIn_normalized_differentialWindows_0.05.txt.gz |
503.9 Mb |
(ftp)(http) |
TXT |
| GSE159620_HL60_JQ1.vs.HL60_DMSO_DESeq2_diff_0.05.txt.gz |
346.6 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_JQ1.vs.HL60_SAHA_JQ1_DESeq2_diff_0.05.txt.gz |
350.4 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_SAHA.vs.HL60_DMSO_DESeq2_diff_0.05.txt.gz |
421.5 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_SAHA.vs.HL60_JQ1_DESeq2_diff_0.05.txt.gz |
431.6 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_SAHA.vs.HL60_SAHA_JQ1_DESeq2_diff_0.05.txt.gz |
369.9 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_SAHA_JQ1.vs.HL60_DMSO_DESeq2_diff_0.05.txt.gz |
482.5 Kb |
(ftp)(http) |
TXT |
| GSE159620_HL60_combined_RNA_expression_matrix.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE159620_RAW.tar |
25.5 Gb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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