Genome-wide localization of histone variants in Toxoplasma gondii implicates variant exchange in stage-specific gene expression

NARDELLI SC; SILMON DE MONERRI NC; VANAGAS L; WANG X; TAMPAKI Z; SULLIVAN WJ; ANGEL SO; KIM K

BMC GENOMICS

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2022

1471-2164

Background: Toxoplasma gondii is a protozoan parasite that differentiates fromacute tachyzoite stages to latent bradyzoite forms in response to environmental cuesthat modify the epigenome. We studied the distribution of the histone variantsCenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatinimmunoprecipitation to understand the role of variant histones in developmentaltransitions of T. gondii parasites.Results: H3.3 and H2A.X were detected in telomere and telomere associatedsequences, whereas H3.3, H2A.X and CenH3 were enriched in centromeres.Histones H2A.Z and H2B.Z colocalize with the transcriptional activation markH3K4me3 in promoter regions surrounding the nucleosome-free region upstream ofthe transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the genebodies of genes that are silent but poised for activation, including bradyzoite stagespecific genes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap,consistent with variant histones demarcating specific functional regions of chromatin.The extent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entiregene (5?UTR and gene body) reflects the timing of gene expression during the cellcycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during thetachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimerdefines active and developmentally silenced regions of the T. gondii epigenomeincluding genes that are poised for expression.