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| Status |
Public on Nov 09, 2022 |
| Title |
PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking (ATAC-Seq) |
| Organism |
Drosophila melanogaster |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The Polycomb repression machinery in Drosophila comprises PRC1 that monoubiquitinates histone H2A at lysine 118 (H2Aub1) and PR-DUB, a major H2Aub1 deubiquitinase, but how H2Aub1 levels must be balanced for Polycomb repression remains enigmatic. We show that H2Aub1 is enriched at Polycomb target genes in early embryos but depleted from these genes during developmental stages when PRC1 represses their transcription. Accordingly, Polycomb targets remain repressed in H2Aub1-deficient animals. In PR-DUB catalytic mutants, high-level H2Aub1 accumulation at Polycomb targets increases chromatin accessibility, consistent with disruption of chromatin fiber folding by H2Aub1 in vitro. Consequently, PR-DUB mutants show defective Polycomb repression, while general transcription is largely unperturbed by the genome-wide, low-level H2Aub1 increase. Changes in H2Aub1 levels alter H3K27 methylation-kinetics but PRC2 nevertheless generates canonical H3K27me3 domains in PRC1 or PR-DUB catalytic mutants. PR-DUB therefore acts as a rheostat that removes excessive H2Aub1 that, though deposited by PRC1, antagonizes PRC1-mediated chromatin compaction.
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| Overall design |
Analysis of ATAC-seq profiles generated from wild-type and mutant Drosophila embryos.
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| Contributor(s) |
Müller J, Bonnet J |
| Citation(s) |
36357125 |
| |
| Submission date |
Aug 01, 2022 |
| Last update date |
Jan 13, 2023 |
| Contact name |
Jürg Müller |
| Organization name |
Max Planck Institute of Biochemistry
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| Street address |
Am Klopferspitz
|
| City |
Martinsried |
| State/province |
Bavaria |
| ZIP/Postal code |
82152 |
| Country |
Germany |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (3) |
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| This SubSeries is part of SuperSeries: |
| GSE210236 |
PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking |
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| Relations |
| BioProject |
PRJNA864798 |
