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| Status |
Public on Nov 26, 2014 |
| Title |
Histone chaperone HIRA orchestrates H4K16ac-decorated dynamic chromatin in senescent cells and is required for suppression of oncogene-induced neoplasia. |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Histone chaperone HIRA deposits nucleosome-destabilizing histone variant H3.3 into chromatin in a DNA replication-independent manner. Histone H3.3 and a subset of other typically “replication-dependent” core histones were expressed in non-proliferating senescent cells, the latter linked to alternative mRNA splicing and polyadenylation. Senescent cells incorporated newly-synthesized histones into chromatin, partially dependent on HIRA. HIRA and newly-deposited histone H3.3 co-localized at promoters of expressed genes, and their distribution shifted between proliferating and senescent cells, paralleling changes in gene expression. In senescent cells, gene promoters showed exceptional enrichment of a histone acetylation linked to open and dynamic chromatin, H4K16ac. Abundance of H4K16ac depended on HIRA. In the mouse, inactivation of HIRA downregulated H4K16ac and dramatically enhanced oncogene-induced hyperplasia. To conclude, HIRA controls a previously undefined dynamic non-canonical H4K16ac-decorated chromatin landscape in senescence, and also plays an unanticipated role in suppression of oncogene-induced neoplasia.
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| Overall design |
Examination of HIRA protein binding alongside histone modification H4K16ac and H3.3 in proliferating and senescent IMR90 cells
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| Contributor(s) |
Rai TS, Cole JJ, Adams PD |
| Citation(s) |
25512559, 27457071 |
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| Submission date |
Mar 27, 2014 |
| Last update date |
Apr 02, 2020 |
| Contact name |
Peter Adams |
| Organization name |
University of Glasgow, Beatson Institute for Cancer Research
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| Street address |
Switchback Rd, Bearsden
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| City |
Glasgow |
| ZIP/Postal code |
G61 1BD |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA242935 |
| SRA |
SRP040680 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56307_H4K16ac-Prolif-2Rep.bed.gz |
99.5 Kb |
(ftp)(http) |
BED |
| GSE56307_H4K16ac.DiffBind.csv.gz |
1.9 Mb |
(ftp)(http) |
CSV |
| GSE56307_H4K16ac.Senes.2Rep.bed.gz |
400.9 Kb |
(ftp)(http) |
BED |
| GSE56307_RAW.tar |
5.6 Gb |
(http)(custom) |
TAR (of BED, BIGWIG) |
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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