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

Guillaume Bordet,Alexei V Tulin,Danping Guo,Niraj Lodhi,Andrew Kossenkov

doi:10.1038/s41598-020-78116-5

Abstract

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.

Highlights

Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation, among other processes
We collected a mixture of 150 male and female third instar larvae for the parp-1C03256 and yellow white strains, hereinafter noted as the parp1−/− and wild type groups, respectively
Expressed genes (DEGs) were identified based on the following criteria: (1) the fold difference had to be higher than two, (2) a two-tailed t-test based on the change of expression between the wild-type and parp-1−/− groups relative to the standard deviation of all measurements had to show a p value lower than 0.05, and (3) the False Discovery Rate (FDR) had to be lower than 15%

Summary

Introduction

Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme involved in DNA repair and transcription regulation, among other processes. 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 poly(ADP-ribose) polymerase (PARP) enzyme family has been extensively studied during the last two decades Recognized for their role in DNA r epair[1], PARPs have been shown to be involved in many other biological processes, including chromatin structure regulation, as well as transcriptional and translational activation and repression[2,3]. The most studied member of this family is PARP-1 This 116 kDa nuclear protein is responsible for the majority of poly(ADP-ribose) (PAR) syntheses in both mammals and Drosophila[8]. We observed that genes downregulated in the absence of PARP-1 generally belonged to functional groups other than those of the upregulated genes

Methods

Results

Conclusion