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| Status |
Public on Feb 19, 2021 |
| Title |
Impaired CHD6 function links misregulation of autophagy and DNA damage response to premature ageing [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Members of the Chromodomain-Helicase-DNA binding (CHD) protein family are chromatin remodelers critically implicated in human pathologies. CHD6 is the least studied member of this family, and we were motivated to dissect its in-cell roles by discovering a mutated CHD6 allele in a patient suffering from the rare Hallermann-Streiff premature aging syndrome (HSS). We generated isogenic iPSC lines carrying (or not) this single point mutation in the CHD6 SANT/SLIDE domain, which allow studying HSS-relevant cell identities. Using these lines, we show for the first time that CHD6 binds the promoters of a cohort of autophagy and stress response genes across cell types. This CHD6 mutation impairs its ability to recruit co-factors and regulate genes in response to DNA damage and autophagy stimulation, thus leading to accumulation of unresolved DNA damage burden. By combining genomics and functional assays, we describe a molecular mechanism underlying chromatin control of autophagic flux and genotoxic stress surveillance that is broadly applicable to human cell types and can explain HSS establishment.
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| Overall design |
polyA enriched 3'-end RNA sequencing of iPS cell lines upon etoposide treatment, starvation and culturing normal conditions.
polyA-enriched mRNA profiles of iPS derived neural crest cells and cardiomyocytes with or without mutated CHD6 protein.
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| Contributor(s) |
Kargapolova Y, Papantonis A |
| Citation(s) |
34021162 |
| |
| Submission date |
Aug 14, 2019 |
| Last update date |
May 24, 2021 |
| Contact name |
Yulia Kargapolova |
| Organization name |
Cologne University
|
| Department |
CMMC
|
| Lab |
AG Papantonis
|
| Street address |
Robert-Koch-Straße 21
|
| City |
Cologne |
| ZIP/Postal code |
50931 |
| Country |
Germany |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (32)
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| This SubSeries is part of SuperSeries: |
| GSE161120 |
Impaired CHD6 function links misregulation of autophagy and DNA damage response to premature ageing |
|
| Relations |
| BioProject |
PRJNA560229 |
| SRA |
SRP218341 |
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