Disordered sequences of transcription factors regulate genomic binding by integrating diverse sequence grammars and...

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Intrinsically disordered regions (IDRs) lack stable structures but are crucial for protein function.
• Transcription factors (TFs) utilize IDRs to interact with DNA and regulate gene expression.
• Understanding how IDRs mediate specific DNA binding remains a key challenge.

Purpose of the Study:

• To investigate how intrinsically disordered regions (IDRs) of the transcription factor Gln3 encode complex genomic binding patterns.
• To identify the mechanisms by which Gln3 binding preferences are regulated under different conditions.

Main Methods:

• Utilized targeted mutagenesis in the transcription factor Gln3.
• Investigated the roles of short linear motifs (SLiMs) and co-binding transcription factors (e.g., Hap2).
• Analyzed amino acid composition within IDRs for binding determinants.

Main Results:

• Identified IDR-embedded determinants that direct Gln3 binding to specific promoter groups.
• Demonstrated that SLiMs and co-binding TFs (Hap2) stabilize Gln3 at respiration-chain promoters.
• Showed that Gln3 binding at nitrogen-associated promoters is determined by IDR amino acid composition, independent of SLiMs or co-binding TFs.

Conclusions:

• TF IDRs can encode complex genomic binding patterns through a combination of SLiM-mediated and composition-encoded interactions.
• IDRs offer a versatile mechanism for regulating TF binding specificity and environmental responsiveness.