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Article Dans Une Revue Epigenetics & Chromatin Année : 2023

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

L. Mahrik
  • Fonction : Auteur
B. Stefanovie
  • Fonction : Auteur
A. Maresova
  • Fonction : Auteur
J. Princova
  • Fonction : Auteur
P. Kolesar
  • Fonction : Auteur
E. Lelkes
  • Fonction : Auteur
C. Faux
  • Fonction : Auteur
M. Prevorovsky
  • Fonction : Auteur
J J Palecek
  • Fonction : Auteur

Résumé

Abstract Background 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. Results 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 Δ gcn5 mutant. The SMC5/6 foci formed normally in Δ 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 Δ gcn5 and Δ ada2 mutants. The drop in SMC5/6 levels was also observed in gcn5 -E191Q acetyltransferase-dead mutant. Conclusion 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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Dates et versions

hal-04236229 , version 1 (10-10-2023)

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L. Mahrik, B. Stefanovie, A. Maresova, J. Princova, P. Kolesar, et al.. The SAGA histone acetyltransferase module targets SMC5/6 to specific genes. Epigenetics & Chromatin, 2023, 16 (1), pp.6. ⟨10.1186/s13072-023-00480-z⟩. ⟨hal-04236229⟩
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