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

Data download
http://resources-molpara.vetmed.lmu.de/Kraus_et_al_2019_sequencing_analysis.tar.gz

Contents of the tar.gz archive:
upload_sequencing/
├── bin/
│   ├── scripts necessary to run the pipeline
├── input/
│   ├── input files
├── output/
│   ├── output files for ChIP and RNA-seq
└── output2/
    └── output files for ATAC-seq

Abstract
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 histone 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 identify 58 histone modifications enriched at transcription start sites (TSSs). Furthermore, we find 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.