The role of variant histone H2AV in Drosophila melanogaster larval hematopoiesis
The role of variant histone H2AV in Drosophila melanogaster larval hematopoiesis
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DOI：
10.1242/dev.142729
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发表时间：
2017-04-15
期刊：
影响因子：
4.6
通讯作者：
Lipsick, Joseph S.
中科院分区：
文献类型：
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作者：
Grigorian, Melina;DeBruhl, Heather;Lipsick, Joseph S.
不依赖于复制的组蛋白变体可以取代典型的依赖于复制的组蛋白。脊椎动物具有多种 H2A 变体组蛋白，包括大多数真核生物中存在的 H2AZ 和 H2AX。 H2AZ 调节转录激活以及基因沉默的维持，而 H2AX 在 DNA 损伤修复中很重要。果蝇果蝇只有一种组蛋白H2A变体（H2AV），它是H2AZ和H2AX的嵌合体。在这项研究中，我们发现 H2AV 的缺乏导致果蝇三龄幼虫形成黑色素团。这些肿块的形成与大部分初级淋巴腺叶的损失有关。有趣的是，后信号传导中心的细胞在这些突变体中得以保留。通过RNAi敲除降低H2AV水平导致较温和的表型，保留了淋巴腺结构，但包括位于淋巴腺髓质区和次级叶内的原血细胞的过早分化。突变拯救实验表明，H2AV 的 H2AZ 样功能而非 H2AX 样功能主要是正常造血所必需的。
Replication-independent histone variants can replace the canonical replication-dependent histones. Vertebrates have multiple H2A variant histones, including H2AZ and H2AX that are present in most eukaryotes. H2AZ regulates transcriptional activation as well as the maintenance of gene silencing, while H2AX is important in DNA damage repair. The fruit fly Drosophila melanogaster has only one histone H2A variant (H2AV), which is a chimera of H2AZ and H2AX. In this study we found that lack of H2AV led to the formation of black melanotic masses in Drosophila third instar larvae. The formation of these masses was found in conjunction with a loss of the majority of the primary lymph gland lobes. Interestingly, the cells of the posterior signaling center were preserved in these mutants. Reduction of H2AV levels by RNAi knockdown caused a milder phenotype that preserved the lymph gland structure but that included precocious differentiation of the prohemocytes located within the medullary zone and the secondary lobes of the lymph gland. Mutant rescue experiments suggest that the H2AZ-like rather than the H2AX-like function of H2AV is primarily required for normal hematopoiesis.