Poly(ADP-ribose) polymerase 1 in genome-wide expression control in Drosophila.

Poly(ADP-ribose) polymerase 1 in genome-wide expression control in Drosophila.
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DOI:
10.1038/s41598-020-78116-5
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发表时间:
2020-12-03
期刊:
影响因子:
4.6
通讯作者:
Tulin AV
Tulin AV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bordet G;Lodhi N;Guo D;Kossenkov A;Tulin AV

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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作与PARP-1活性的失调有关。尽管在过去的几十年里进行了深入的研究,但PARP-1在转录调控中的作用仍然没有得到很好的理解。在这项研究中,转录组学分析在果蝇三龄幼虫进行。共鉴定了602个基因,在体内不存在PARP-1的情况下,其表达水平显示出大规模的变化。在这些基因中,存在几个功能基因组,包括转录因子和细胞色素家族成员。来自相同功能组的基因的转录水平以类似的方式受到PARP-1缺失的影响。在没有PARP-1的情况下,所有编码转录因子的失调基因都下调,而编码细胞色素P450家族成员的所有基因都上调。细胞色素P450蛋白含有血红素作为辅因子,并参与氧化还原。在不存在PARP-1的情况下,还观察到几种移动的元件的表达的显著变化,表明PARP-1可能参与调节移动的元件的表达。
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.
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