Poly(ADP-ribosyl)ating enzymes cooperate to coordinate development

Abstract

The transcriptome is subject to rapid and massive changes during the transition between developmental stages. These changes require tight control to avoid the undesired reactivation of gene expression that is only important for previous developmental stages and, if unchecked during transition between developmental stages, could lead to anarchic proliferation and formation of malignant tumors. In this context, the involvement of chromatin factors is important since they can directly regulate the expression of multiple genes at the same time. Poly(ADP-ribose) enzymes, involved in several processes from DNA repair to transcription regulation, might play a role in this regulation. Here, we report that PARP-1 and PARG cooperate to temporally regulate the gene expression profile during the larval/pupa transition. PARP-1 and PARG are both essential in repressing the expression of genes coding for digestive enzymes and larval cuticle proteins, while PARG positively regulate the expression of defense response genes. These results suggest a cooperative coordination between PARP-1 and PARG that specifically maintains the integrity of expression profile between developmental stages.

Poly(ADP-ribosyl)ating enzymes coordinate metabolic rewiring with developmental progression

“…4B). These results, in addition to those of our previous study (14), show that PARG and PARP1 play both direct and complementary roles to regulate the transcription program involved in the transition from larval to pupal stage.…”

“…Interestingly, we found that PARG and PARP1 bind together to the promoter region of the transcription factors involved in ecdysone mid-response (Supplemental Table S1). Their expression is not signi cantly affected in parg and parp1 mutants, but most are downregulated (14). Together, these results suggest that PARP1 and PARG might play a role in the ecdysone mid-response.…”

“…We previously reported that 20-hydroxyecdysone, an effector in the ecdysone pathway (29), can activate PARP1 activity (12). Furthermore, we previously showed that the expression of genes coding for enzymes involved in the synthesis of 20-hydroxyecdysone are not affected during L3 larval puff stage 7-9 in parg and parp1 mutant (14), suggesting that PARP1 acts downstream ecdysone rather than upstream. Additionally, the expression of glue genes, which are located within puffs of polytene chromosomes and belong to the early response to ecdysone pathway that starts during L3 larval puff stage 7-9 (30), are still initiated in both parg and parp1 mutants, suggesting that PARP1 does not affect ecdysone early-response genes.…”

“…Conversely, poly(ADP-ribose) glycohydrolase (PARG) reverses PARP1 activity by removing poly(ADP-ribose) moieties from acceptor proteins (11,12,13). Recent studies have revealed a complementary, rather than antagonistic, relationship between PARG and PARP1 (12,14,15,16). Upon activation, PARP1 undergoes automodi cation and dissociates from chromatin, leading to its inactivation (8,17,18).…”

“…In fruit ies, both Parp1 C03256 hypomorph and Parg 27.1 null mutants result in developmental arrest at the end of the third instar larval stage (L3 larva puff stage 7-9) (11,18), resulting to a population of third instar larvae animals not able to complete their development but that are still alive (7). Previous ndings suggest that both PARG and PARP1 regulate the transcription of developmental genes during the larva-topupa transition (14). However, the precise interaction between PARG and chromatin, particularly in the context of protein recruitment, remains to be elucidated, given that PARG lacks a DNA-binding domain (DBD) and seems to interact with chromatin only to a limited extent (19), the speci c interaction between PARG and chromatin in the context of the protein's recruitment remains to be elucidated.…”