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| Status |
Public on Jun 29, 2018 |
| Title |
Facultative dosage compensation of developmental genes on autosomes in Drosophila and mammals [RIP-seq] |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Haploinsufficiency and aneuploidy are two phenomena, where alteration of gene dosage causes severe cellular defects ultimately resulting in developmental failures and disease. One remarkable exception is the X chromosome, where copy number differences between males and females are buffered through the action of dosage compensation systems. In Drosophila, the Male-Specific Lethal complex (MSLc) mediates two-fold upregulation of the single male X chromosome via Histone H4 lysine 16 acetylation (H4K16ac). The evolutionary origin and conservation of this process orchestrated by MSL2, the only male-specific protein within the fly MSLc, have remained unclear. Here, we report that MSL2, in addition to its function on the X, targets dosage-sensitive autosomal genes involved in patterning and morphogenesis. We show that the precise regulation of these genes by MSL2 is required for proper development of the fly wing. This set of dosage sensitive genes maintained such regulation during evolution, as MSL2 binds and similarly regulates mouse orthologues via deposition of H4K16ac. We propose that MSL2-mediated H4K16ac is an evolutionarily conserved process mediating gene-by-gene dosage compensation across flies and mammals.
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| Overall design |
Genome-wide RNA interaction profiles (FLASH; Fast cloning of RNA After some Sort of affinity purification for High-throughput sequencing) of MSL2 and MLE in Drosophila melanogaster third instar larvae. Males and females separated, 2 biological replicates each.
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| Contributor(s) |
Valsecchi CI, Semplicio G, Akhtar A |
| Citation(s) |
31601616 |
| |
| Submission date |
Jan 30, 2018 |
| Last update date |
Nov 25, 2019 |
| Contact name |
Asifa Akhtar |
| E-mail(s) |
[email protected]
|
| Organization name |
Max Planck Institute of Immunobiology and Epigenetics
|
| Department |
Chromatin Regulation
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| Lab |
Akhtar Lab
|
| Street address |
Stuebeweg 51
|
| City |
Freiburg |
| ZIP/Postal code |
79108 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
| GPL23323 |
Illumina HiSeq 3000 (Drosophila melanogaster) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE109901 |
Facultative dosage compensation of developmental genes on autosomes in Drosophila and mammals |
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| Relations |
| BioProject |
PRJNA432261 |
| SRA |
SRP131813 |
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