摘要Nuclear proteins are major constituents and key regulators of nucleome topological organization and ma-nipulators of nuclear events.To decipher the global connectivity of nuclear proteins and the hierarchically organized modules of their interactions,we conducted two rounds of cross-linking mass spectrometry(XL-MS)analysis,one of which followed a quantitative double chemical cross-linking mass spectrometry(in vivo qXL-MS)workflow,and identified 24,140 unique crosslinks in total from the nuclei of soybean seed-lings.This in vivo quantitative interactomics enabled the identification of 5340 crosslinks that can be con-verted into 1297 nuclear protein-protein interactions(PPIs),1220(94％)of which were non-confirmative(or novel)nuclear PPIs compared with those in repositories.There were 250 and 26 novel interactors of his-tones and the nucleolar box C/D small nucleolar ribonucleoprotein complex,respectively.Modulomic anal-ysis of orthologous Arabidopsis PPIs produced 27 and 24 master nuclear PPI modules(NPIMs)that contain the condensate-forming protein(s)and the intrinsically disordered region-containing proteins,respec-tively.These NPIMs successfully captured previously reported nuclear protein complexes and nuclear bodies in the nucleus.Surprisingly,these NPIMs were hierarchically assorted into four higher-order com-munities in a nucleomic graph,including genome and nucleolus communities.This combinatorial pipeline of 4C quantitative interactomics and PPI network modularization revealed 17 ethylene-specific module var-iants that participate in a broad range of nuclear events.The pipeline was able to capture both nuclear pro-tein complexes and nuclear bodies,construct the topological architectures of PPI modules and module variants in the nucleome,and probably map the protein compositions of biomolecular condensates.