J 2023

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

MAHRÍK, Lenka, Barbora ŠTEFANOVIE, Anna MARESOVA, Jarmila PRINCOVA, Peter KOLESÁR et. al.

Basic information

Original name

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

Authors

MAHRÍK, Lenka (703 Slovakia, belonging to the institution), Barbora ŠTEFANOVIE (703 Slovakia, belonging to the institution), Anna MARESOVA (203 Czech Republic), Jarmila PRINCOVA (203 Czech Republic), Peter KOLESÁR (703 Slovakia, belonging to the institution), Edit LELKES (703 Slovakia, belonging to the institution), Celline FAUX (250 France), Dominique HELMLINGER (250 France), Martin PREVOROVSKY (203 Czech Republic) and Jan PALEČEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

EPIGENETICS & CHROMATIN, LONDON, BMC, 2023, 1756-8935

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.900 in 2022

RIV identification code

RIV/00216224:14310/23:00130526

Organization unit

Faculty of Science

UT WoS

000944569400001

Keywords in English

Genetic and protein-protein interactions; SMC5/6 complex; Nse3 KITE; SAGA histone acetyltransferase module; Gcn5; Ada2; Chromatin accessibility; DNA repair; rDNA; Gene regions

Tags

Tags

International impact, Reviewed
Změněno: 5/3/2024 09:23, Mgr. Eva Dubská

Abstract

V originále

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.

Links

LM2018132, research and development project
Name: Národní centrum lékařské genomiky (Acronym: NCLG)
Investor: Ministry of Education, Youth and Sports of the CR, National Center for Medical Genomics
LTC20033, research and development project
Name: The SMC5/6 complex in nucleome organization (Acronym: Nukleom)
Investor: Ministry of Education, Youth and Sports of the CR, INTER-COST
MUNI/R/1142/2021, interní kód MU
Name: Visualization of the 3D structure of chromatin
Investor: Masaryk University, CAREER RESTART
MUNI/R/1262/2022, interní kód MU
Name: Vztah mezi opravou DNA a transkripcí
Investor: Masaryk University, Crosstalk between DNA repair and transcription, CAREER RESTART