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用人源H2A.Z直系同源物替换拟南芥H2A.Z揭示了广泛的功能保守性以及N端尾部序列对拟南芥发育的重要性有限。

Replacement of Arabidopsis H2A.Z with human H2A.Z orthologs reveals extensive functional conservation and limited importance of the N-terminal tail sequence for Arabidopsis development.

作者信息

Sijacic Paja, Holder Dylan H, Silver Brianna D, Krall Ellen G, Willett Courtney G, Foroozani Maryam, Deal Roger B

机构信息

Department of Biology, Emory University, Atlanta, GA 30322, USA.

Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, GA 30322, USA.

出版信息

Genetics. 2025 Apr 3. doi: 10.1093/genetics/iyaf065.

DOI:10.1093/genetics/iyaf065
PMID:40179256
Abstract

The incorporation of histone variants, distinct paralogs of core histones, into chromatin affects all DNA-templated processes in the cell, including the regulation of transcription. In recent years, much research has been focused on H2A.Z, an evolutionarily conserved H2A variant found in all eukaryotes. In order to investigate the functional conservation of H2A.Z histones during eukaryotic evolution we transformed h2a.z deficient Arabidopsis thaliana plants with each of the three human H2A.Z variants to assess their ability to rescue the mutant defects. We discovered that human H2A.Z.1 and H2A.Z.2.1 fully complement the phenotypic abnormalities of h2a.z plants despite significant divergence in the N-terminal tail sequences of Arabidopsis and human H2A.Zs. In contrast, the brain-specific splice variant H2A.Z.2.2 has a dominant-negative effect in wild-type plants, mimicking an H2A.Z deficiency phenotype. Furthermore, human H2A.Z.1 almost completely re-establishes normal H2A.Z chromatin occupancy in h2a.z plants and restores the expression of more than 84% of misexpressed genes. Finally, we used a series of N-terminal tail truncations of Arabidopsis HTA11 to reveal that the N-terminal tail of Arabidopsis H2A.Z is not necessary for normal plant development under optimal growth conditions but does play an important role in mounting proper abiotic stress responses.

摘要

组蛋白变体(核心组蛋白的不同旁系同源物)掺入染色质会影响细胞中所有以DNA为模板的过程,包括转录调控。近年来,许多研究都集中在H2A.Z上,它是在所有真核生物中都存在的一种进化上保守的H2A变体。为了研究真核生物进化过程中H2A.Z组蛋白的功能保守性,我们用三种人类H2A.Z变体分别转化h2a.z缺陷型拟南芥植株,以评估它们挽救突变缺陷的能力。我们发现,尽管拟南芥和人类H2A.Z的N端尾部序列存在显著差异,但人类H2A.Z.1和H2A.Z.2.1完全弥补了h2a.z植株的表型异常。相比之下,脑特异性剪接变体H2A.Z.2.2在野生型植株中具有显性负效应,模拟了H2A.Z缺陷表型。此外,人类H2A.Z.1几乎完全重新建立了h2a.z植株中正常的H2A.Z染色质占据情况,并恢复了超过84%的异常表达基因的表达。最后,我们使用了一系列拟南芥HTA11的N端尾部截短来揭示,在最佳生长条件下,拟南芥H2A.Z的N端尾部对于正常植物发育不是必需的,但在应对适当的非生物胁迫反应中确实起着重要作用。

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2
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本文引用的文献

1
A near-complete assembly of an Arabidopsis thaliana genome.一个拟南芥基因组的近乎完整的组装。
Mol Plant. 2022 Aug 1;15(8):1247-1250. doi: 10.1016/j.molp.2022.05.014. Epub 2022 Jun 1.
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H2A.Z's 'social' network: functional partners of an enigmatic histone variant.H2A.Z 的“社交”网络:一个神秘组蛋白变体的功能伙伴。
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The H2A.Z-nucleosome code in mammals: emerging functions.哺乳动物中的H2A.Z核小体编码:新出现的功能
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Histone Variants in the Specialization of Plant Chromatin.植物染色质特化中的组蛋白变体
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NuA4 and H2A.Z control environmental responses and autotrophic growth in Arabidopsis.NuA4 和 H2A.Z 控制拟南芥的环境响应和自养生长。
Nat Commun. 2022 Jan 12;13(1):277. doi: 10.1038/s41467-021-27882-5.
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What makes a histone variant a variant: Changing H2A to become H2A.Z.是什么让组蛋白变体成为变体:将 H2A 变成 H2A.Z。
PLoS Genet. 2021 Dec 6;17(12):e1009950. doi: 10.1371/journal.pgen.1009950. eCollection 2021 Dec.
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Structural basis of chromatin regulation by histone variant H2A.Z.组蛋白变体 H2A.Z 调控染色质的结构基础。
Nucleic Acids Res. 2021 Nov 8;49(19):11379-11391. doi: 10.1093/nar/gkab907.
8
Non-redundant functions of H2A.Z.1 and H2A.Z.2 in chromosome segregation and cell cycle progression.H2A.Z.1 和 H2A.Z.2 在染色体分离和细胞周期进程中的非冗余功能。
EMBO Rep. 2021 Nov 4;22(11):e52061. doi: 10.15252/embr.202052061. Epub 2021 Aug 23.
9
Histone variants at a glance.组蛋白变体速览。
J Cell Sci. 2021 Mar 26;134(6):jcs244749. doi: 10.1242/jcs.244749.
10
Histone variants take center stage in shaping the epigenome.组蛋白变体在塑造表观基因组中占据中心舞台。
Curr Opin Plant Biol. 2021 Jun;61:101991. doi: 10.1016/j.pbi.2020.101991. Epub 2021 Jan 9.