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弓形虫组蛋白变体的全基因组定位提示变体交换在特定阶段的基因表达中起作用。

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

机构信息

Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.

Present address: Instituto Carlos Chagas/Fiocruz-PR, Curitiba, PR, CEP 81.350-010, Brazil.

出版信息

BMC Genomics. 2022 Feb 14;23(1):128. doi: 10.1186/s12864-022-08338-6.

DOI:10.1186/s12864-022-08338-6
PMID:35164683
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8842566/
Abstract

BACKGROUND

Toxoplasma gondii is a protozoan parasite that differentiates from acute tachyzoite stages to latent bradyzoite forms in response to environmental cues that modify the epigenome. We studied the distribution of the histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatin immunoprecipitation to understand the role of variant histones in developmental transitions of T. gondii parasites.

RESULTS

H3.3 and H2A.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 colocalize with the transcriptional activation mark H3K4me3 in promoter regions surrounding the nucleosome-free region upstream of the transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genes that are silent but poised for activation, including bradyzoite stage-specific 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 entire gene (5'UTR and gene body) reflects the timing of gene expression during the cell cycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during the tachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes that are poised for expression.

CONCLUSIONS

Histone variants mark functional regions of parasite genomes with the dynamic placement of the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator of parasite and eukaryotic differentiation.

摘要

背景

弓形虫是一种原生动物寄生虫，它会根据改变表观基因组的环境线索，从急性速殖子阶段分化为潜伏的缓殖子形式。我们通过全基因组染色质免疫沉淀研究了组蛋白变体 CenH3、H3.3、H2A.X、H2A.Z 和 H2B.Z 的分布，以了解变体组蛋白在弓形虫寄生虫发育转变中的作用。

结果

H3.3 和 H2A.X 检测到在端粒和端粒相关序列中，而 H3.3、H2A.X 和 CenH3 在着丝粒中富集。组蛋白 H2A.Z 和 H2B.Z 与转录激活标记 H3K4me3 在转录起始位点上游无核小体区域的启动子区域共定位。H2B.Z/H2A.Z 组蛋白对处于沉默但准备激活的基因的基因体也定位，包括缓殖子阶段特异性基因。大多数 H2A.X 和 H2A.Z/H2B.Z 位点不重叠，与变体组蛋白标记染色质特定功能区域一致。H2A.Z/H2B.Z（和 H3.3 和 H2A.X）在整个基因（5'UTR 和基因体）内的富集程度反映了细胞周期中基因表达的时间，表明 H2B.Z/H2A.Z 的动态周转发生在速殖子细胞周期中。因此，变体组蛋白 H2A.Z/H2B.Z 二聚体的分布定义了弓形虫表观基因组的活性和发育沉默区域，包括准备表达的基因。

结论

组蛋白变体标记寄生虫基因组的功能区域，动态放置的 H2A.Z/H2B.Z 二聚体被认为是寄生虫和真核生物分化的保守调节因子。

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