Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen 6525GA, the Netherlands.
Mol Microbiol. 2013 Mar;87(5):1061-73. doi: 10.1111/mmi.12151. Epub 2013 Jan 28.
Histone variants are key components of the epigenetic code and evolved to perform specific functions in transcriptional regulation, DNA repair, chromosome segregation and other fundamental processes. Although variants for histone H2A and H3 are found throughout the eukaryotic kingdom, variants of histone H2B and H4 are rarely encountered. H2B.Z is one of those rare H2B variants and is apicomplexan-specific. Here we show that in Plasmodium falciparum H2B.Z localizes to euchromatic intergenic regions throughout intraerythrocytic development and together with H2A.Z forms a double-variant nucleosome subtype. These nucleosomes are enriched in promoters over 3' intergenic regions and their occupancy generally correlates with the strength of the promoter, but not with its temporal activity. Remarkably, H2B.Z occupancy levels exhibit a clear correlation with the base-composition of the underlying DNA, raising the intriguing possibility that the extreme AT content of the intergenic regions within the Plasmodium genome might be instructive for histone variant deposition. In summary, our data show that the H2A.Z/H2B.Z double-variant nucleosome demarcates putative regulatory regions of the P. falciparum epigenome and likely provides a scaffold for dynamic regulation of gene expression in this deadly human pathogen.
组蛋白变体是表观遗传密码的关键组成部分，它们进化到能够在转录调控、DNA 修复、染色体分离和其他基本过程中执行特定的功能。虽然在真核生物王国中发现了组蛋白 H2A 和 H3 的变体，但组蛋白 H2B 和 H4 的变体很少遇到。H2B.Z 就是其中一种罕见的 H2B 变体，并且是疟原虫特异性的。在这里，我们表明在疟原虫中，H2B.Z 定位于整个红细胞内发育过程中的常染色质基因间区，并与 H2A.Z 一起形成双变体核小体亚型。这些核小体富含 3'基因间区的启动子，其占有率通常与启动子的强度相关，而与启动子的时间活性无关。值得注意的是，H2B.Z 占有率与基础 DNA 的碱基组成明显相关，这提出了一个有趣的可能性，即在疟原虫基因组中基因间区的极端 AT 含量可能对组蛋白变体沉积具有指导作用。总之，我们的数据表明，H2A.Z/H2B.Z 双变体核小体标记了疟原虫表观基因组的潜在调节区域，并可能为该致命人类病原体中基因表达的动态调节提供了一个支架。
