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Kraus, A.J. ; Vanselow, J.T.* ; Lamer, S.* ; Brink, B.G.* ; Schlosser, A.* ; Siegel, T.N.*

Distinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes.

Nat. Commun. 11:1498 (2020)
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Open Access Gold
Creative Commons Lizenzvertrag
Despite histone H2A variants and acetylation of histones occurring in almost every eukaryotic organism, it has been difficult to establish direct functional links between canonical histones or H2A variant acetylation, deposition of H2A variants and transcription. To disentangle these complex interdependent processes, we devised a highly sensitive strategy for quantifying histone acetylation levels at specific genomic loci. Taking advantage of the unusual genome organization in Trypanosoma brucei, we identified 58 histone modifications enriched at transcription start sites (TSSs). Furthermore, we found TSS-associated H4 and H2A.Z acetylation to be mediated by two different histone acetyltransferases, HAT2 and HAT1, respectively. Whereas depletion of HAT2 decreases H2A.Z deposition and shifts the site of transcription initiation, depletion of HAT1 does not affect H2A.Z deposition but reduces total mRNA levels by 50%. Thus, specifically reducing H4 or H2A.Z acetylation levels enabled us to reveal distinct roles for these modifications in H2A.Z deposition and RNA transcription. Histone modification and deposition are key regulators of transcription. Here, Kraus et al. provide a quantitative histone acetylome for Trypanosoma brucei, identify histone modifications enriched at transcription start sites, and show how H4 and H2A.Z acetylation affect histone deposition and transcription in trypanosomes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Double-stranded-rna; Acetyltransferase Complex; Histone Modifications; Chromatin-structure; Genome; Variant; Protein; Expression; Exchange; Nua4
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 1498 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Grants Bioinformatics Core Facility at the Biomedical Center Munich
Young Investigator Program of the Research Center for Infectious Diseases (ZINF) at the University of Wurzburg, Germany
German Research Foundation
ERC