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| Status |
Public on Jun 08, 2023 |
| Title |
ASH1L methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair [ATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
To recognize DNA damage, nucleotide excision repair (NER) deploys a multipart mechanism by which the XPC sensor detects helical distortions followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place on chromatin where DNA is wrapped around histones. We show that the histone methyltransferase ASH1L, once activated by MRG15, accelerates global-genome NER activity. Upon UV irradiation, ASH1L deposits H3K4me3 marks all over the genome (except in gene promoters), thus priming chromatin for relocations of XPC from native to damaged DNA. ASH1L further recruits the histone chaperone FACT to UV lesions. In the absence of ASH1L, MRG15 or FACT, XPC persists on damaged DNA without being able to deliver lesions to the TFIIH verifier. We conclude that ASH1L implements repair hotspots whose H3K4me3 and FACT occupancy confers an active promoter-like code and organization of histones that make DNA damage verifiable by the NER machinery.
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| Overall design |
Assay for transposase-accessible chromatin using sequencing (ATAC-seq) was performed in wild type and ASH1L knockout U2OS cells either untreated (not exposed to UV) or 3 hours after UV treatment.
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| Contributor(s) |
Maritz C, Yancoskie MN, Diethelm S, Khaleghi R, Brülisauer S, Ferreira NS, Jiang Y, Sturla SJ, Naegeli H |
| Citation(s) |
37393406 |
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| Submission date |
Mar 09, 2023 |
| Last update date |
Jul 03, 2023 |
| Contact name |
Michelle Yancoskie |
| Organization name |
Institute of Veterinary Pharmacology and Toxicology, University of Zurich
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| Department |
Vetsuisse Faculty
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| Lab |
Naegeli Lab
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| Street address |
Winterthurerstr. 260
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| City |
Zurich |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| GSM7089925 |
U2OS wildtype cells, no UV, biol rep1 |
| GSM7089926 |
U2OS wildtype cells, no UV, biol rep2 |
| GSM7089927 |
U2OS wildtype cells, 3h post UV, biol rep1 |
| GSM7089928 |
U2OS wildtype cells, 3h post UV, biol rep2 |
| GSM7089929 |
U2OS ASH1L knockout cells, no UV, biol rep1 |
| GSM7089930 |
U2OS ASH1L knockout, no UV, biol rep2 |
| GSM7089931 |
U2OS ASH1L knockout, 3h post UV, biol rep1 |
| GSM7089932 |
U2OS ASH1L knockout, 3h post UV, biol rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE227009 |
ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair |
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| Relations |
| BioProject |
PRJNA942903 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE227007_RAW.tar |
5.1 Gb |
(http)(custom) |
TAR (of BW, NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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