biostudies-literatureLi XNCRR NIH HHSNIGMS NIH HHS1982-5https://www.ebi.ac.uk/biostudies/studies/S-EPMC3520067biostudies-literatureUnknown134(4)Post-translational modifications (PTMs) (e.g., acetylation, methylation, and phosphorylation) play crucial roles in regulating the diverse protein-protein interactions involved in essentially every cellular process. While significant progress has been made to detect PTMs, profiling protein-protein interactions mediated by these PTMs remains a challenge. Here, we report a method that combines a photo-cross-linking strategy with stable isotope labeling in cell culture (SILAC)-based quantitative mass spectrometry to identify PTM-dependent protein-protein interactions. To develop and apply this approach, we focused on trimethylated lysine-4 at the histone H3 N-terminus (H3K4Me(3)), a PTM linked to actively transcribed gene promoters. Our approach identified proteins previously known to recogniJournal of the American Chemical SocietyQuantitative chemical proteomics approach to identify post-translational modification-mediated protein-protein interactions.PMC3520067R01 GM098579-01RR00862R01 GM098579R01 GM098579-02GM98579Li XLi YChait BTKapoor TMMolloy KRFoley EAfalseQuantitative chemical proteomics approach to identify post-translational modification-mediated protein-protein interactions.Post-translational modifications (PTMs) (e.g., acetylation, methylation, and phosphorylation) play crucial roles in regulating the diverse protein-protein interactions involved in essentially every cellular process. While significant progress has been made to detect PTMs, profiling protein-protein interactions mediated by these PTMs remains a challenge. Here, we report a method that combines a photo-cross-linking strategy with stable isotope labeling in cell culture (SILAC)-based quantitative mass spectrometry to identify PTM-dependent protein-protein interactions. To develop and apply this approach, we focused on trimethylated lysine-4 at the histone H3 N-terminus (H3K4Me(3)), a PTM linked to actively transcribed gene promoters. Our approach identified proteins previously known to recogni2012-01-01T00:00:00Z2012 Feb2025-04-26T10:45:10.206Z2019-03-27T01:01:42ZS-EPMC35200672223932010.1021/ja210528v