GSE98806
Chromosomal organization and genic expression in Apicomplexan parasites is critically dictated by a versatile acetylation-methylation switch at K31 on the lateral surface of histone H4
A striking unusual genome architecture characterizes the two related human parasitic pathogens Plasmodium falciparum and Toxoplasma gondii. A major fraction of the bulk parasite genome is packaged as transcriptionally permissive euchromatin with few loci embedded in silenced heterochromatin. Primary chromatin shapers include histone modifications at the nucleosome lateral surface close to the DNA but their mode of action remains unclear. We identify versatile modifications at Lys31 within the globular domain of histone H4 as key determinants of genome organization and expression in Apicomplexa. H4K31 acetylation promotes a relaxed chromatin state at the promoter of active genes through nucleosome disassembly in both parasites. In contrast, monomethylated H4K31 is enriched in the core body of Toxoplasma active genes but inversely correlates with transcription while being astonishingly enriched at transcriptionally inactive pericentromeric heterochromatin in Plasmodium. This is the first evidence for a methylated residue of H4 associating with transcriptional regulation likely by reducing histone turnover hence slowing RNA polymerase progression across transcribed loci. Overall design: We report genome-wide H3K9me3, H3K4me1, H3K4me3, H3K14ac, H4K31ac, H4K31me1, H4K20me3 profiles in Toxoplasma gondii using ChIP-seq