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

SHEILA NARDELLI*; NATALIE C. SILMON DE MONERRI; LAURA VANAGAS; XIAONAN WANG; ZOI TAMPAKI; WILLIAM J. SULLIVAN JR.; SERGIO O. ANGEL; KAMI KIM

BMC GENOMICS

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2022

1471-2164

Background: Toxoplasma gondii is a protozoan parasite that differentiatesfrom acute tachyzoite stages to latent bradyzoite forms in response toenvironmental cues that modify the epigenome. We studied the distribution ofthe histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-widechromatin immunoprecipitation to understand the role of variant histones indevelopmental transitions of T. gondii parasites.. Results: H3.3 andH2A.X were detected in telomere and telomere associated sequences, whereas H3.3,H2A.X and CenH3 were enriched in centromeres. Histones H2A.Z and H2B.Z colocalizewith the transcriptional activation mark H3K4me3 in promoter regionssurrounding the nucleosome-free region upstream of the transcription startsite. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genesthat are silent but poised for activation, including bradyzoite stage-specificgenes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap, consistentwith variant histones demarcating specific functional regions of chromatin. Theextent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entire gene(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 histoneH2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes thatare poised for expression.Conclusions: Histonevariants mark functional regions of parasite genomes with the dynamic placementof the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator ofparasite and eukaryotic differentiation.