PARP-1 cooperates with histone methyltransferase to regulate transcription

Abstract

PARP-1 is central to transcriptional regulation under both normal and heat stress conditions, with the governing mechanisms yet to be fully understood. Biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. PR-Set7, the sole H4K20 mono-methylase, and PARP-1 mutants undergo developmental arrest during larval-pupal shift in Drosophila . RNA-seq analysis showed a positive correlation between PR-Set7-and PARP-1-dependent gene expression in third-instar larvae, suggesting co-regulation during developmental phases. During heat stress, PARP-1 repositions from the Hsp70 promoter to its gene body, facilitating gene activation. PARP-1 and PR-Set7 are essential for activating Hsp70 and a subset of heat shock genes during heat stress, with a notable increase of H4K20me1 at their gene body. We propose that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of specific genes during both development and heat stress.