The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development.
The Drosophila heterochromatic gene encoding poly(ADP-ribose) polymerase (PARP) is required to modulate chromatin structure during development.
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DOI：
10.1101/gad.1003902
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发表时间：
2002-08
影响因子：
10.5
通讯作者：
A. Tulin;Dianne Stewart;A. Spradling
中科院分区：
文献类型：
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作者：
A. Tulin;Dianne Stewart;A. Spradling
聚ADP核糖聚合酶（Poly（ADP-ribose）polymerase，PARP）是一种重要的NAD依赖性修饰酶，介导DNA修复、转录和凋亡的重要步骤，但其在发育过程中的作用尚不清楚。我们发现，一个单一的果蝇Parp基因跨越超过150 kb的转座子丰富的着丝粒异染色质，并产生几个差异剪接的成绩单，包括一个新的异构体，PARP-e，预测编码缺乏酶活性的蛋白质。Parp-e上游启动子附近的插入突变破坏所有Parp表达。异染色质而非常染色质序列对微球菌核酸酶变得超敏感，核仁不能形成，copia反转录转座子的转录水平升高超过50倍;某些转基因的多样化表达显著增强。通过表达编码PARP-e的cDNA，可以挽救幼虫致死率并恢复PARP活性。我们建议，PARP-e自动调节PARP转录影响其异染色质环境的染色质结构。我们的研究结果表明，Parp起着组织果蝇染色质结构的基本作用。
Poly(ADP-ribose) polymerase (PARP) is a major NAD-dependent modifying enzyme that mediates important steps in DNA repair, transcription, and apoptosis, but its role during development is poorly understood. We found that a single Drosophila Parp gene spans more than 150 kb of transposon-rich centromeric heterochromatin and produces several differentially spliced transcripts, including a novel isoform, PARP-e, predicted to encode a protein lacking enzymatic activity. An insertion mutation near the upstream promoter for Parp-e disrupts all Parp expression. Heterochromatic but not euchromatic sequences become hypersensitive to micrococcal nuclease, nucleoli fail to form, and transcript levels of the copia retrotransposon are elevated more than 50-fold; the variegated expression of certain transgenes is dominantly enhanced. Larval lethality can be rescued and PARP activity restored by expressing a cDNA encoding PARP-e. We propose that PARP-e autoregulates Parp transcription by influencing the chromatin structure of its heterochromatic environment. Our results indicate that Parp plays a fundamental role organizing the structure of Drosophila chromatin.