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

Area of Science:

• Molecular Biology
• Bioinformatics
• Genomics

Background:

• Transcription regulation is complex and challenging to annotate in Gene Ontology.
• Transcription coregulators (coTF) play a vital role in gene regulation by linking DNA-binding transcription factors (dbTFs) to regulatory elements.
• Identifying novel coTFs is crucial for a comprehensive understanding of transcriptional control.

Purpose of the Study:

• To identify unannotated, putative transcription coregulators within human protein complexes.
• To expand the set of known coTFs for improved Gene Ontology (GO) annotation.
• To establish a foundation for future wet-lab validation and annotation initiatives.

Main Methods:

• Mining CORUM and hu.MAP databases for known and presumed human transcription coregulators.
• Analyzing BioGRID and IntAct databases for interactors of 1457 human dbTFs.
• Developing a prioritization score based on GO annotations and interactome data.

Main Results:

• Identified 1093 putative transcription factor coregulator complex subunits.
• Confirmed direct interaction with a dbTF for 954 of these subunits.
• Substantially expanded the pool of potential coTFs for 'transcription coregulator activity' annotation.

Conclusions:

• The study successfully identified a large number of novel putative transcription coregulators.
• These findings facilitate the annotation of 'transcription coregulator activity' and related complexes.
• The developed prioritization score aids in focusing future research and wet-lab validation efforts.