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| Status |
Public on Jun 22, 2019 |
| Title |
Cockayne syndrome group B deficiency reduces H3K9me3 chromatin remodeler SETDB1 and exacerbates cellular aging |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cockayne syndrome (CS) is an accelerated aging disorder, caused by mutations in the CSA or CSB genes. In CSB-deficient cells, poly (ADP ribose) polymerase (PARP) is persistently activated by unrepaired DNA damage and PARP consumes and depletes cellular nicotinamide adenine dinucleotide (NAD), which leads to mitochondrial dysfunction. Here, the distribution of poly (ADP ribose) (PAR) was determined in CSB-deficient cells using ADPr-ChAP (ADP ribose-chromatin affinity purification), and the results show striking enrichment of PAR at transcription start sites (TSS), depletion of heterochromatin, and downregulation of H3K9me3-specific methyltransferases SUV39H1 and SETDB1. Induced-expression of SETDB1 in CSB-deficient cells downregulated PAR and normalized mitochondrial function. The results suggest that defects in CSB are strongly associated with loss of heterochromatin, downregulation of SETDB1, increased PAR in highly-transcribed regions, and mitochondrial dysfunction.
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| Overall design |
H3K9me3 ChIP or ADPr-ChAP was performed from CSB-deficient (CS1AN) /control cells (CS1AN expressing wild type CSB) or doxycyclin-induced SETDB1 expressing CSB-deficient cells.
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| Contributor(s) |
Lee J, Demarest TG, Babbar M, Kim EW, Okur MN, De S, Croteau DL, Bohr VA |
| Citation(s) |
31276581 |
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| Submission date |
Jun 21, 2019 |
| Last update date |
Oct 15, 2019 |
| Contact name |
Jong-Hyuk Lee |
| E-mail(s) |
[email protected]
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| Organization name |
National Institute of Health
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| Lab |
Laboratory of Molecular Gerontology
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| Street address |
251 Bayview BLVD
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA550140 |
| SRA |
SRP202559 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE133176_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of BED, BIGWIG, BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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