Cooperative targeting of PARP-1 domains to regulate metabolic and developmental genes.

PARP-1, also known as poly(ADP-ribose) polymerase 1, is a multifunctional nuclear enzyme that plays a critical role in transcriptional regulation through its three functional domains: the N-terminal DNA-binding domain (DBD) containing two zinc fingers for DNA binding and a third zinc finger for maintaining interdomain contacts, the auto modification domain (AD), and the C-terminal domain, which includes the protein-interacting WGR domain and the catalytic domain. Despite the critical role that PARP-1 plays in regulating gene expression, the mechanisms by which it is targeted to chromatin are not well understood. In this study, we aimed to understand the targeting of PARP-1 to chromatin using ChIP-seq of YFP-tagged deletional isoforms of PARP-1 (ZnI, ZnII, AD-WGR) and a construct that lacks only ZnI (ΔZnI). Our results indicate that other PARP-1 domains are sufficient to target PARP-1 to active genes in the absence of ZnI. Furthermore, we found that PARP-1 represses metabolic gene pathways and activates developmental gene pathways. The results of ChIP-seq analysis showed that PARP-1 and ΔZnI were preferentially bound to the gene bodies of PARP-1-regulated metabolic genes compared to developmental genes. PARP-1 domains (ZnI, ZnII and AD-WGR) also preferentially occupied the gene bodies of PARP-1-regulated metabolic genes, however, they were more enriched at the TSS of PARP-1-regulated developmental genes compared to metabolic genes. Thus, we propose that PARP-1 domains cooperatively target PARP-1 to PARP-1-regulated genes to coordinate metabolic and developmental gene expression programs.

Informations de copyright

Copyright © 2023 Bamgbose, Johnson and Tulin.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.