Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, 501 North Columbia Road, Stop 9061, Grand Forks, ND, 58202, USA.
Fox Chase Cancer Center, Philadelphia, PA, USA.
Sci Rep. 2020 Dec 3;10(1):21151. doi: 10.1038/s41598-020-78116-5.
Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation, among other processes. Malignant transformations, tumor progression, the onset of some neuropathies and other disorders have been linked to misregulation of PARP-1 activity. Despite intensive studies during the last few decades, the role of PARP-1 in transcription regulation is still not well understood. In this study, a transcriptomic analysis in Drosophila melanogaster third instar larvae was carried out. A total of 602 genes were identified, showing large-scale changes in their expression levels in the absence of PARP-1 in vivo. Among these genes, several functional gene groups were present, including transcription factors and cytochrome family members. The transcription levels of genes from the same functional group were affected by the absence of PARP-1 in a similar manner. In the absence of PARP-1, all misregulated genes coding for transcription factors were downregulated, whereas all genes coding for members of the cytochrome P450 family were upregulated. The cytochrome P450 proteins contain heme as a cofactor and are involved in oxidoreduction. Significant changes were also observed in the expression of several mobile elements in the absence of PARP-1, suggesting that PARP-1 may be involved in regulating the expression of mobile elements.
聚(ADP-核糖)聚合酶 1(PARP-1)是一种参与 DNA 修复和转录调控等过程的核酶。恶性转化、肿瘤进展、某些神经病变和其他疾病的发生与 PARP-1 活性的失调有关。尽管在过去几十年进行了深入研究,但 PARP-1 在转录调控中的作用仍未得到很好的理解。在这项研究中,对黑腹果蝇三龄幼虫进行了转录组分析。共鉴定出 602 个基因,这些基因在体内缺乏 PARP-1 的情况下其表达水平发生了大规模变化。在这些基因中,存在几个功能基因群,包括转录因子和细胞色素家族成员。来自同一功能群的基因的转录水平因缺乏 PARP-1 而以相似的方式受到影响。在缺乏 PARP-1 的情况下,所有编码转录因子的失调基因均下调,而所有编码细胞色素 P450 家族成员的基因均上调。细胞色素 P450 蛋白含有血红素作为辅因子,参与氧化还原反应。在缺乏 PARP-1 的情况下,还观察到几个移动元件的表达发生了显著变化,这表明 PARP-1 可能参与调节移动元件的表达。