Abstract
Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation. Here, we identify 6703 and 1536 protein–protein interactions for 109 different human TFs through proximity-dependent biotinylation (BioID) and affinity purification mass spectrometry (AP-MS), respectively. The BioID analysis identifies more high-confidence interactions, highlighting the transient and dynamic nature of many of the TF interactions. By performing clustering and correlation analyses, we identify subgroups of TFs associated with specific biological functions, such as RNA splicing or chromatin remodeling. We also observe 202 TF-TF interactions, of which 118 are interactions with nuclear factor 1 (NFI) family members, indicating uncharacterized cross-talk between NFI signaling and other TF signaling pathways. Moreover, TF interactions with basal transcription machinery are mainly observed through TFIID and SAGA complexes. This study provides a rich resource of human TF interactions and also act as a starting point for future studies aimed at understanding TF-mediated transcription.
Highlights
Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation
TFs were found to interact with proteins involved in chromatin remodeling, transcription, mRNA splicing, and RNA processing, highlighting the cooperative nature and close proximity of these processes
The Mediator complex, SAGA complex, and most general TFs (GTFs) are multimeric protein complexes that are needed for polymerase II (Pol-II) promoter recognition and transcription initiation[40,41,42]
Summary
Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation. While the binding of TFs to DNA is relatively well studied, for the most part, we still lack a global understanding of TF protein–protein interactions (PPIs) and their roles in the regulation of transcription. These interactions paint a picture of how transcription factors are activated or repressed and add experimental evidence for the potential relevance of transient interactions in the advent of transcriptionrelated nuclear condensates and phase separation This large interactome network of TFs allowed us to recognize several interactome subgroups of TFs, such as TFs linked to mRNA splicing and TFs linked to chromatin remodeling. This work represents a rich resource to direct future studies aimed at understanding TFmediated transcription and how TF-formed interactions regulate important cellular phenomena in both health and disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
