The domino SWI2/SNF2 Gene Product Represses Cell Death in Drosophila melanogaster.
The domino SWI2/SNF2 Gene Product Represses Cell Death in Drosophila melanogaster.
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DOI：
10.1534/g3.118.200228
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发表时间：
2018-07-02
期刊：
影响因子：
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通讯作者：
Yedvobnick B
中科院分区：
文献类型：
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作者：
Ellis K;Wardwell-Ozgo J;Moberg KH;Yedvobnick B
果蝇domino基因座编码SWI 2/SNF 2类DNA依赖性ATP酶。这类染色质重塑与一系列细胞活动相关，包括转录、复制、修复和重组。此外，多米诺骨牌最初被观察到保持一个抑制染色质状态，通过遗传相互作用的研究与同源异型基因。虽然多米诺骨牌突变也具有细胞死亡表型的特征，但其与死亡途径的相关性尚未研究。在这里，我们使用靶向RNA干扰来抑制翅膀中的多米诺骨牌功能。由此产生的翅损伤表型被发现通过促凋亡基因座的过度表达而增强，并且通过这些基因座的功能丧失而抑制。翼缘和叶片组织的损失与效应器Caspase Dcp-1的激活相关，Caspase Dcp-1是细胞凋亡的标志物。受影响的翅膀区域也表现出较低水平的DIAP 1蛋白，一种细胞凋亡抑制剂。较低水平的DIAP 1蛋白与DIAP 1基因转基因报告基因（线程-LacZ）的活性的影响不相关，这表明DIAP 1的损失发生在转录后。在某些情况下，还观察到通过BrdU掺入测量的靶组织内的过度细胞增殖。最后，我们使用了一个转基因报告构建监测染色质状态上游的促凋亡reaper位点。在表现出靶向多米诺骨牌损失和翅表型的基因型中，我们观察到仅在受影响区域中报告活性增加。这些数据支持这样的结论，多米诺骨牌正常功能，以维持在一个压抑状态的促凋亡基因。
The Drosophila domino locus encodes DNA-dependent ATPases of the SWI2/SNF2 class. This class of chromatin remodeler is associated with an array of cellular activities encompassing transcription, replication, repair and recombination. Moreover, domino was observed initially to maintain a repressive chromatin state via genetic interaction studies with homeotic genes. Although domino mutations were also characterized with a cell death phenotype, its association with a death pathway has not been investigated. Here we have used targeted RNA interference to depress domino function in the wing. Resultant wing damage phenotypes were found to be enhanced through overexpression of pro-apoptotic loci, and suppressed through loss of function of these loci. Loss of wing margin and blade tissue was correlated with activation of the effector Caspase Dcp-1, a marker for apoptosis. The affected wing regions also exhibited lower levels of the DIAP1 protein, an inhibitor of apoptosis. The lower level of DIAP1 protein was not correlated with an effect on the activity of a DIAP1 gene transgenic reporter (thread-LacZ), suggesting that loss of DIAP1 occurred post transcriptionally. In some cases excessive cell proliferation within the targeted tissue, measured through BrdU incorporation, was also observed. Finally, we used a transgenic reporter construct to monitor the chromatin state upstream of the proapoptotic reaper locus. In genotypes exhibiting targeted domino loss and wing phenotypes, we observed increased reporter activity only in the affected areas. These data support the conclusion that domino normally functions to maintain pro-apoptotic genes in a repressed state.
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影响因子：
12.4
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影响因子：
4.5
作者：
Prado, Jose Rafael Morillo;Srinivasan, Shrividhya;Fuller, Margaret T.
通讯作者：
Fuller, Margaret T.
影响因子：
1.6
作者：
Schirling, Corinna;Heseding, Christiane;Ehrenhofer-Murray, Ann E.
通讯作者：
Ehrenhofer-Murray, Ann E.
DOI：
10.1038/nrm3735
发表时间：
2014-02
期刊：
Nature reviews. Molecular cell biology
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影响因子：
8
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