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| Status |
Public on Apr 14, 2021 |
| Title |
DNAJC9 Integrates Heat Shock Molecular Chaperones into the Histone Chaperone Network |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
From biosynthesis to assembly into nucleosomes, histones are handed through a cascade of histone chaperones, which shield histones from non-specific interactions. Whether mechanisms exist to safeguard the histone fold during histone chaperone handover events or to release trapped intermediates is unclear. Using structure-guided and functional proteomics, we identify and characterize a histone chaperone function of DNAJC9, a heat shock co-chaperone that promotes HSP70-mediated catalysis. We elucidate the structure of DNAJC9, in a histone H3-H4 co-chaperone complex with MCM2, revealing how this dual histone and heat shock co-chaperone binds histone substrates. We show that DNAJC9 recruits HSP70-type enzymes via its J domain to fold histone H3-H4 substrates: upstream in the histone supply chain, during replication- and transcription-coupled nucleosome assembly, and to clean up spurious interactions. With its dual functionality, DNAJC9 integrates ATP-resourced protein folding into the histone supply pathway to resolve aberrant intermediates throughout the dynamic lives of histones.
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| Overall design |
Quantitative ChIP-seq analysis of DNAJC9 distribution and abundance from cells expressing DNAJC9-MYC-Flag WT, J or 4A mutants, and control cells . All experiments were done in duplicates. Chromatin of Drosophila melanogater S2 cells were used as spike-in for normalization purpose.
Please note that each processed data was generated from both replicates (R1 and R2) and is linked to the corresponding R1 sample records.
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| Contributor(s) |
Hammond C, Reverón-Gómez N, Groth A |
| Citation(s) |
33857403 |
| |
| Submission date |
Jul 14, 2020 |
| Last update date |
Apr 17, 2021 |
| Contact name |
Anja Groth |
| E-mail(s) |
anja.groth@cpr.ku.dk
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| Organization name |
Novo Nordisk Foundation Center for Protein Research
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| Street address |
Blegdamsvej 3B
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA646272 |
| SRA |
SRP271863 |
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