A shift in chromatin binding of phosphorylated p38 precedes transcriptional changes upon oxidative stress

FEBS Lett. 2024 Dec;598(23):2926-2938. doi: 10.1002/1873-3468.15006. Epub 2024 Sep 1.

Abstract

P38 mitogen-activated protein kinases are key in the regulation of the cellular response to stressors. P38 is known to regulate transcription, mRNA processing, stability, and translation. The transcriptional changes mediated by phosphorylated p38 (P-p38) in response to extracellular stimuli have been thoroughly analyzed in many tissues and organisms. However, the genomic localization of chromatin-associated P-p38 remains poorly understood. Here, we analyze the chromatin binding of activated P-p38 and its role in the response to reactive oxygen species (ROS) in Drosophila S2 cells. We found that P-p38 is already bound to chromatin in basal conditions. After ROS exposure, chromatin-associated P-p38 relocates towards genes involved in the recovery process. Our findings highlight the role of P-p38 dynamic chromatin binding in orchestrating gene expression responses to oxidative stress.

Keywords: Drosophila; ROS; p38; stress; transcription.

MeSH terms

  • Animals
  • Cell Line
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation
  • Oxidative Stress*
  • Phosphorylation
  • Protein Binding
  • Reactive Oxygen Species / metabolism
  • Transcription, Genetic*
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • Chromatin
  • p38 Mitogen-Activated Protein Kinases
  • Reactive Oxygen Species
  • Drosophila Proteins