The SAGA histone acetyltransferase module targets SMC5/6 to specific genes
| Authors | |
|---|---|
| Year of publication | 2023 |
| Type | Article in Periodical |
| Magazine / Source | EPIGENETICS & CHROMATIN |
| MU Faculty or unit | |
| Citation | |
| web | https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-023-00480-z |
| Doi | http://dx.doi.org/10.1186/s13072-023-00480-z |
| Keywords | Genetic and protein-protein interactions; SMC5/6 complex; Nse3 KITE; SAGA histone acetyltransferase module; Gcn5; Ada2; Chromatin accessibility; DNA repair; rDNA; Gene regions |
| Description | Structural Maintenance of Chromosomes (SMC) complexes are molecular machines driving chromatin organization at higher levels. In eukaryotes, three SMC complexes (cohesin, condensin and SMC5/6) play key roles in cohesion, condensation, replication, transcription and DNA repair. Their physical binding to DNA requires accessible chromatin. We performed a genetic screen in fission yeast to identify novel factors required for SMC5/6 binding to DNA. We identified 79 genes of which histone acetyltransferases (HATs) were the most represented. Genetic and phenotypic analyses suggested a particularly strong functional relationship between the SMC5/6 and SAGA complexes. Furthermore, several SMC5/6 subunits physically interacted with SAGA HAT module components Gcn5 and Ada2. As Gcn5-dependent acetylation facilitates the accessibility of chromatin to DNA-repair proteins, we first analysed the formation of DNA-damage-induced SMC5/6 foci in the Delta gcn5 mutant. The SMC5/6 foci formed normally in Delta gcn5, suggesting SAGA-independent SMC5/6 localization to DNA-damaged sites. Next, we used Nse4-FLAG chromatin-immunoprecipitation (ChIP-seq) analysis in unchallenged cells to assess SMC5/6 distribution. A significant portion of SMC5/6 accumulated within gene regions in wild-type cells, which was reduced in Delta gcn5 and Delta ada2 mutants. The drop in SMC5/6 levels was also observed in gcn5-E191Q acetyltransferase-dead mutant. Our data show genetic and physical interactions between SMC5/6 and SAGA complexes. The ChIP-seq analysis suggests that SAGA HAT module targets SMC5/6 to specific gene regions and facilitates their accessibility for SMC5/6 loading. |
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