|
| Status |
Public on Feb 22, 2021 |
| Title |
Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology [ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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, with CHD6 being one of its least studied members. Here, we discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. We show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS-mutation affects CHD6 protein folding and impairs its ability to recruit co-factors in response to DNA damage or autophagy stimulation. This leads to an accumulation of DNA damage burden and to senescence-like phenotypes. By combining genomics and functional assays, we describe for the first time a molecular mechanism for the chromatin control of autophagic flux and genotoxic stress surveillance that applies broadly to human cell types and explains HSS onset.
|
| |
|
| Overall design |
Assay for Transposase-Accessible Chromatin using sequencing in iPS cells
|
| |
|
| Contributor(s) |
Papantonis A, Übelmesser N, Josipovic N, Hugo T |
| Citation(s) |
34021162 |
| |
| Submission date |
Nov 09, 2020 |
| Last update date |
Oct 15, 2021 |
| Contact name |
Argyris Papantonis |
| E-mail(s) |
[email protected]
|
| Organization name |
University Medical Center Goettingen
|
| Department |
Department of Pathology
|
| Street address |
Robert-Koch-Str 40
|
| City |
Goettingen |
| ZIP/Postal code |
37075 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (4)
|
|
| This SubSeries is part of SuperSeries: |
| GSE161120 |
Impaired CHD6 function links misregulation of autophagy and DNA damage response to premature ageing |
|
| Relations |
| BioProject |
PRJNA675611 |
| SRA |
SRP291753 |
Less...
More...