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| Status |
Public on Sep 24, 2021 |
| Title |
ATAD2 maintains the equilibrium between nucleosome assembly and disassembly |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
To avoid toxic histone overload, histone deposition and removal must be finely tuned. Following a series of functional studies in human, mouse and S. pombe, we show here that the AAA ATPase ATAD2 is a conserved mediator of histone removal and a regulator of histone deposition. In Atad2 knockout (KO) spermatogenic cells, the late-stage genome-wide eviction of histones and their replacement by protamines are significantly delayed. In S. pombe, deletion of abo1 leads to a dramatic decrease in cell growth, with the appearance of suppressor clones recovering normal growth. Identification of the corresponding suppressor mutations revealed that the causes of cell toxicity are mainly the deregulated activity of the histone chaperone HIRA and histone overload. We also show that, in Atad2 KO mouse ES cells, HIRA and FACT are trapped on nucleosomes at transcription start sites of active genes, resulting in histone overload and abnormal histone deposition on nucleosome-free regions. Overall, these data shed new light on a need for energy-consuming auxiliary factors, such as ATAD2, to maintain a balanced and dynamic histone chaperone basal activity and to avoid a deleterious histone overload.
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| Overall design |
ChIP-seq experiments with HIRA and SSRP1 antibodies in wild type (WT) and ATAD2 KO (KO) embryonic stem (ES) cells
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| Contributor(s) |
Rousseaux S, Chuffart F, Wang T, Barral S, Puthier D, Bargier L, Khochbin S |
| Citation(s) |
34580178 |
| Submission date |
Jun 22, 2021 |
| Last update date |
Sep 29, 2021 |
| Contact name |
Sophie Rousseaux |
| Organization name |
INSERM-UGA
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| Department |
IAB
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| Lab |
U1209
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| Street address |
Bd de la Chantourne
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| City |
La Tronche |
| ZIP/Postal code |
38706 |
| Country |
France |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA739885 |
| SRA |
SRP325024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE178647_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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