Analysis of the Human Endogenous Coregulator Complexome

SummaryElucidation of endogenous cellular protein-protein interactions and their networks is most desirable for biological studies. Here we report our study of endogenous human coregulator protein complex networks obtained from integrative mass spectrometry-based analysis of 3290 affinity purifications. By preserving weak protein interactions during complex isolation and utilizing high levels of reciprocity in the large dataset, we identified many unreported protein associations, such as a transcriptional network formed by ZMYND8, ZNF687, and ZNF592. Furthermore, our work revealed a tiered interplay within networks that share common proteins, providing a conceptual organization of a cellular proteome composed of minimal endogenous modules (MEMOs), complex isoforms (uniCOREs), and regulatory complex-complex interaction networks (CCIs). This resource will effectively fill a void in linking correlative genomic studies with an understanding of transcriptional regulatory protein functions within the proteome for formulation and testing of future hypotheses.

Graphical AbstractFigure optionsDownload high-quality image (366 K)Download as PowerPoint slideHighlights
► Database of endogenous coregulator complexes containing >10,000 unique proteins
► Analytical approach preserves weaker complex-complex interaction networks
► Many transcriptional coregulators promiscuously share multiple interaction networks
► Protein complex units are hubs for diverse genomic alterations of polygenic diseases