Intrinsically Disordered Regions Direct Transcription Factor In Vivo Binding Specificity

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Transcription factors (TFs) bind specific DNA motifs in vitro but target distinct promoters in vivo.
• Intrinsically disordered regions (IDRs) are common in TFs and are known for promiscuous interactions.
• The role of IDRs in achieving specific TF binding site selection in vivo remains unclear.

Purpose of the Study:

• To investigate the role of intrinsically disordered regions (IDRs) in the in vivo promoter specificity of transcription factors (TFs).
• To determine if IDRs are necessary and sufficient for TF localization to target promoters.
• To explore the mechanism by which IDRs contribute to specific TF binding.

Main Methods:

• Studied Msn2 and Yap1, transcription factors with long IDRs outside their DNA-binding domains.
• Assessed the necessity and sufficiency of IDRs for promoter localization.
• Analyzed the conservation of IDR-mediated specificity across orthologs.

Main Results:

• IDRs were found to be both necessary and sufficient for the localization of Msn2 and Yap1 to the majority of their target promoters.
• IDR-directed binding specificity is mediated by numerous weak interactions distributed across the IDR sequence, not by a single localized domain.
• The specificity conferred by IDRs is conserved between evolutionarily distant TF orthologs.

Conclusions:

• Intrinsically disordered regions (IDRs) play a crucial role in directing transcription factors (TFs) to specific promoter regions in vivo.
• The distributed weak interaction network within IDRs allows for rapid and specific TF binding-site detection.
• IDRs are a key mechanism for achieving promoter specificity in transcription factors.