Integration of transcription coregulator complexes with sequence-specific DNA-binding factor interactomes

The domain of transcription regulation has been notoriously difficult to annotate in the Gene Ontology, partly because of the intricacies of gene regulation which involve molecular interactions with DNA as well as amongst protein complexes. The molecular function 'transcription coregulator activity' is a part of the biological process 'regulation of transcription, DNA-templated' that occurs in the cellular component 'chromatin'. It can mechanistically link sequence-specific DNA-binding transcription factor (dbTF) regulatory DNA target sites to coactivator and corepressor target sites through the molecular function 'cis-regulatory region sequence-specific DNA binding'. Many questions arise about transcription coregulators (coTF). Here, we asked how many unannotated, putative coregulators can be identified in protein complexes? Therefore, we mined the CORUM and hu.MAP protein complex databases with known and strongly presumed human transcription coregulators. In addition, we trawled the BioGRID and IntAct molecular interaction databases for interactors of the known 1457 human dbTFs annotated by the GREEKC and GO consortia. This yielded 1093 putative transcription factor coregulator complex subunits, of which 954 interact directly with a dbTF. This substantially expands the set of coTFs that could be annotated to 'transcription coregulator activity' and sets the stage for renewed annotation and wet-lab research efforts. To this end, we devised a prioritisation score based on existing GO annotations of already curated transcription coregulators as well as interactome representation. Since all the proteins that we mined are parts of protein complexes, we propose to concomitantly engage in annotation of the putative transcription coregulator-containing complexes in the Complex Portal database.