Catching global interactions in vivo.

Histone proteins and transcription factors (TFs) play critical roles in gene transcription and development of multicellular organisms. Although antibody mediated protein isolation couple with mass spectrometry approach has been a standard method to identify TF interacting partners and characterize their functional molecular complexes, it becomes urge to develop a robust method to functional characterize how these transcription factors act during biological process in the post-human genome project era. Here, Dr. Zhao and his colleagues in the National Heart, Lung, and Blood Institute of NIH develop a sensitive and robust strategy to globally identify and characterize in vivo protein-protein interactions termed bait protein-protein interaction-sequencing (bPPI-seq) (Zhang et al. in Cell Res doi:10.1038/cr.2017.112, 2017). As a proof-of-principle, they demonstrated that genome-wide interacting partners of histone variant H2A.Z are mainly involved in transcriptional regulation which is distinct from the interacting proteins of canonical histone H2A. Thus, their results suggest that bPPI-seq can be widely used to globally characterize protein complexes especially transcription factor interacting partners and molecular networks formed.