PRC1 Protein Subcomplexes Architecture: Focus on the Interplay between Distinct PCGF Subunits in Protein Interaction Networks

The six PCGF proteins (PCGF1-6) define the biochemical identity of Polycomb repressor complex 1 (PRC1) subcomplexes. While structural and functional studies of PRC1 subcomplexes have revealed their specialized roles in distinct aspects of epigenetic regulation, our understanding of the variation in the protein interaction networks of distinct PCGF subunits in different PRC1 complexes is incomplete. We carried out an affinity purification mass spectrometry (AP-MS) screening of three PCGF subunits, PCGF1 (NSPC1), PCGF2 (MEL18), and PCGF4 (BMI1), to define their interactome and potential cellular function in pluripotent human embryonal carcinoma cell “NT2”. The bioinformatic analysis revealed that these interacting proteins cover a range of functional pathways, often involved in cell biology and chromatin regulation. We also found evidence of mutual regulation (at mRNA and protein level) between three distinct PCGF subunits. Furthermore, we confirmed that the disruption of these subunits results in reduced cell proliferation ability. We reveal an interplay between the compositional diversity of the distinct PCGF containing PRC1 complex and the potential role of PCGF proteins within the wider cellular network.