In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-8), p. e1010514-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010514
DOI:
10.1371/journal.ppat.1010514.g001
DOI:
10.1371/journal.ppat.1010514.g002
DOI:
10.1371/journal.ppat.1010514.g003
DOI:
10.1371/journal.ppat.1010514.g004
DOI:
10.1371/journal.ppat.1010514.g005
DOI:
10.1371/journal.ppat.1010514.g006
DOI:
10.1371/journal.ppat.1010514.g007
DOI:
10.1371/journal.ppat.1010514.g008
DOI:
10.1371/journal.ppat.1010514.t001
DOI:
10.1371/journal.ppat.1010514.t002
DOI:
10.1371/journal.ppat.1010514.s001
DOI:
10.1371/journal.ppat.1010514.s002
DOI:
10.1371/journal.ppat.1010514.s003
DOI:
10.1371/journal.ppat.1010514.s004
DOI:
10.1371/journal.ppat.1010514.s005
DOI:
10.1371/journal.ppat.1010514.r001
DOI:
10.1371/journal.ppat.1010514.r002
DOI:
10.1371/journal.ppat.1010514.r003
DOI:
10.1371/journal.ppat.1010514.r004
DOI:
10.1371/journal.ppat.1010514.r005
DOI:
10.1371/journal.ppat.1010514.r006
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2205412-1
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