Modifications at K31 on the lateral surface of histone H4 contribute to genome structure and expression in apicomplexan parasites

ELife
Fabien SindikubwaboMohamed-Ali Hakimi

Abstract

An 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 now identify versatile modifications at Lys31 within the globular domain of histone H4 that crucially determine genome organization and expression in Apicomplexa parasites. H4K31 acetylation at the promoter correlates with, and perhaps directly regulates, gene expression in both parasites. By contrast, monomethylated H4K31 is enriched in the core body of T. gondii active genes but inversely correlates with transcription, whereas it is unexpectedly enriched at transcriptionally inactive pericentromeric heterochromatin in P. falciparum, a region devoid of the characteristic H3K9me3 histone mark and its downstream effector HP1.

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Citations

Jun 23, 2018·Annual Review of Microbiology·Kami Kim
May 31, 2019·Journal of the American Society for Mass Spectrometry·Matthew V HoltNicolas L Young
Nov 16, 2019·Nucleic Acids Research·Wieteke Anna Maria HoeijmakersRichárd Bártfai
Oct 21, 2019·Gene·Joseph Hannon Bozorgmehr
May 30, 2021·Nature Communications·Kevin CheesemanJonathan B Weitzman

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Datasets Mentioned

BETA
GSE98806
PRJNA386433

Methods Mentioned

BETA
acetylation
Peptide
dot-blot
transfection
histone acetylation
immunoprecipitation
ChIP-seq
RNA-seq
ChIPs
X-ray

Software Mentioned

Off
Mascot
MACS
ZEN
MACS2
Line Basecaller OLB
Activemotif
Array Analyze
Solexa CHASTITY
genome browser IGB

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