Publication details

The SAGA histone acetyltransferase module targets SMC5/6 to specific genes

Investor logo
Authors

MAHRÍK Lenka ŠTEFANOVIE Barbora MARESOVA Anna PRINCOVA Jarmila KOLESÁR Peter LELKES Edit FAUX Celline HELMLINGER Dominique PREVOROVSKY Martin PALEČEK Jan

Year of publication 2023
Type Article in Periodical
Magazine / Source EPIGENETICS & CHROMATIN
MU Faculty or unit

Faculty of Science

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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info