biostudies-literatureHuang YNational Natural Science Foundation of China103934https://www.ebi.ac.uk/biostudies/studies/S-EPMC12681906biostudies-literatureUnknown88Protein S-persulfidation, a post-translational modification mediated by hydrogen sulfide (H₂S), plays an essential role in regulating protein function. However, current profiling methods, mainly based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), tend to detect abundant proteins and often miss low-abundance but important regulators like transcription factors (TFs). To better understand the S-persulfidation landscape, we integrated datasets from three species-Homo sapiens, Mus musculus, and Arabidopsis thaliana-and found that TFs are strikingly underrepresented. To address this gap, we applied oxidative proteomics data from the Oximouse database, which reflects age-related redox changes, and identified hepatocyte nuclear factor 1α (HNF1α) as a candidate S-persulfiRedox biologyFunctional S-persulfidation exploration reveals a novel regulatory mechanism of HNF1α.PMC12681906T24B20158192100181670395Chen NYang JLi JWang CZhang HBu DTang CZhang LWang JCui QWang LLi WPeng HLi ZGeng BJin HHuang YWang SDu JWang YChen SCui CChu MfalseFunctional S-persulfidation exploration reveals a novel regulatory mechanism of HNF1α.Protein S-persulfidation, a post-translational modification mediated by hydrogen sulfide (H₂S), plays an essential role in regulating protein function. However, current profiling methods, mainly based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), tend to detect abundant proteins and often miss low-abundance but important regulators like transcription factors (TFs). To better understand the S-persulfidation landscape, we integrated datasets from three species-Homo sapiens, Mus musculus, and Arabidopsis thaliana-and found that TFs are strikingly underrepresented. To address this gap, we applied oxidative proteomics data from the Oximouse database, which reflects age-related redox changes, and identified hepatocyte nuclear factor 1α (HNF1α) as a candidate S-persulfi2025-01-01T00:00:00Z2025 Nov2026-06-05T23:38:08.243Z2026-05-23T03:13:54.831ZS-EPMC126819064127403610.1016/j.redox.2025.103934