TY  - JOUR
A1  - Vellmer, Tim
A1  - Hartleb, Laura
A1  - Fradera Sola, Albert
A1  - Kramer, Susanne
A1  - Meyer-Natus, Elisabeth
A1  - Butter, Falk
A1  - Janzen, Christian J.
T1  - A novel SNF2 ATPase complex in Trypanosoma brucei with a role in H2A.Z-mediated chromatin remodelling
T2  - PLoS Pathogens
N2  - A cascade of histone acetylation events with subsequent incorporation of a histone H2A variant plays an essential part in transcription regulation in various model organisms. A key player in this cascade is the chromatin remodelling complex SWR1, which replaces the canonical histone H2A with its variant H2A.Z. Transcriptional regulation of polycistronic transcription units in the unicellular parasite Trypanosoma brucei has been shown to be highly dependent on acetylation of H2A.Z, which is mediated by the histone-acetyltransferase HAT2. The chromatin remodelling complex which mediates H2A.Z incorporation is not known and an SWR1 orthologue in trypanosomes has not yet been reported. In this study, we identified and characterised an SWR1-like remodeller complex in T. brucei that is responsible for Pol II-dependent transcriptional regulation. Bioinformatic analysis of potential SNF2 DEAD/Box helicases, the key component of SWR1 complexes, identified a 1211 amino acids-long protein that exhibits key structural characteristics of the SWR1 subfamily. Systematic protein-protein interaction analysis revealed the existence of a novel complex exhibiting key features of an SWR1-like chromatin remodeller. RNAi-mediated depletion of the ATPase subunit of this complex resulted in a significant reduction of H2A.Z incorporation at transcription start sites and a subsequent decrease of steady-state mRNA levels. Furthermore, depletion of SWR1 and RNA-polymerase II (Pol II) caused massive chromatin condensation. The potential function of several proteins associated with the SWR1-like complex and with HAT2, the key factor of H2A.Z incorporation, is discussed.
KW  - Trypanosoma
KW  - chromatin
KW  - histones
KW  - RNA interference
KW  - Trypanosoma brucei gambiense
KW  - luciferase
KW  - transcriptional control
KW  - nucleosomes
Y1  - 2022
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/30137
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-301372
VL  - 18
IS  - 6
ER  -