Deposition of histone variant H2A.Z within gene bodies regulates responsive genes.
Deposition of histone variant H2A.Z within gene bodies regulates responsive genes.
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DOI：
10.1371/journal.pgen.1002988
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Zilberman D
中科院分区：
文献类型：
--
作者：
Coleman-Derr D;Zilberman D
真核染色质的调控依赖于许多表观遗传因素之间的相互作用，包括组蛋白修饰、DNA甲基化和组蛋白变异的结合。H2A。Z是最保守但最神秘的组蛋白变体之一，富集于基因的转录起始位点，与多种染色体过程有关。最近，我们报道了H2A基因与H2A基因之间的全基因组反相关。DNA甲基化是异染色质的表观遗传标志，在植物和动物的活性基因体内也发现了异染色质甲基化。在这里，我们使用一种新的h2a来研究这种反相关的基础。拟南芥的z功能缺失线。通过全基因组亚硫酸盐测序，我们证明了H2A的缺失。在拟南芥中，Z对基因中DNA甲基化的水平或特征只有很小的影响，我们认为DNA甲基化与H2A之间存在全局的反相关关系。Z主要是由于排除了H2A。甲基化DNA中的Z。H2A的RNA测序和基因组定位。Z表示H2A。跨基因体而非TSS的Z富集与较低的转录水平和较高的基因反应性相关。失去H2A。Z导致许多基因的失调，这些基因与对环境和发育刺激的反应不成比例。我们建议H2A。Z在基因体中的沉积促进了基因表达水平和模式的变异性，基因DNA甲基化的一个主要功能是排除H2A。Z来自组成性表达基因。真核生物利用一种被称为组蛋白的高度保守的蛋白质来包装它们的DNA，以适应细胞核。组蛋白是核小体的组成部分，核小体是染色质的基本单位。组蛋白变体是这些蛋白质的特化版本，通过改变核小体的生化特性和相互作用伙伴来改变染色质景观。H2A。Z，一种保守的真核组蛋白变体，优先富集在基因的开始，尽管这种富集的意义尚不清楚。我们和其他人已经证明了H2A。在植物和动物基因组的甲基化DNA中，Z明显缺失。DNA甲基化通常被认为是表观遗传沉默的标志，最近在许多基因的体内被发现。在这里，我们提出证据，DNA甲基化和H2A之间的全基因组反相关。拟南芥中Z的富集是DNA甲基化阻止H2A的结果。Z公司。我们证明了H2A的存在。基因体内的Z与较低的转录水平和跨组织类型和环境条件的表达模式的较高变异性相关，我们认为基因体DNA甲基化的一个主要功能是排除H2A。从高表达和组成性表达的基因的身体。
The regulation of eukaryotic chromatin relies on interactions between many epigenetic factors, including histone modifications, DNA methylation, and the incorporation of histone variants. H2A.Z, one of the most conserved but enigmatic histone variants that is enriched at the transcriptional start sites of genes, has been implicated in a variety of chromosomal processes. Recently, we reported a genome-wide anticorrelation between H2A.Z and DNA methylation, an epigenetic hallmark of heterochromatin that has also been found in the bodies of active genes in plants and animals. Here, we investigate the basis of this anticorrelation using a novel h2a.z loss-of-function line in Arabidopsis thaliana. Through genome-wide bisulfite sequencing, we demonstrate that loss of H2A.Z in Arabidopsis has only a minor effect on the level or profile of DNA methylation in genes, and we propose that the global anticorrelation between DNA methylation and H2A.Z is primarily caused by the exclusion of H2A.Z from methylated DNA. RNA sequencing and genomic mapping of H2A.Z show that H2A.Z enrichment across gene bodies, rather than at the TSS, is correlated with lower transcription levels and higher measures of gene responsiveness. Loss of H2A.Z causes misregulation of many genes that are disproportionately associated with response to environmental and developmental stimuli. We propose that H2A.Z deposition in gene bodies promotes variability in levels and patterns of gene expression, and that a major function of genic DNA methylation is to exclude H2A.Z from constitutively expressed genes. Eukaryotes package their DNA to fit within the nucleus using well-conserved proteins, called histones, that form the building blocks of nucleosomes, the fundamental units of chromatin. Histone variants are specialized versions of these proteins that change the chromatin landscape by altering the biochemical properties and interacting partners of the nucleosome. H2A.Z, a conserved eukaryotic histone variant, is preferentially enriched at the beginnings of genes, though the significance of this enrichment remains unknown. We and others have shown that H2A.Z is conspicuously absent from methylated DNA across the genome in plants and animals. Typically considered a mark of epigenetic silencing, DNA methylation has more recently been discovered in the bodies of many genes. Here, we present evidence that the genome-wide anticorrelation between DNA methylation and H2A.Z enrichment in Arabidopsis is the result of DNA methylation acting to prevent H2A.Z incorporation. We demonstrate that the presence of H2A.Z within gene bodies is correlated with lower transcription levels and higher variability in expression patterns across tissue types and environmental conditions, and we propose that a major function of gene-body DNA methylation is to exclude H2A.Z from the bodies of highly and constitutively expressed genes.
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