START domains generate paralog-specific regulons from a single network architecture

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Genetics

Background:

• Functional divergence of transcription factors (TFs) is crucial for evolution but poorly understood.
• CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) TFs, CORONA (CNA) and PHABULOSA (PHB), are functionally diverged paralogs.

Purpose of the Study:

• Investigate the mechanistic drivers of functional divergence between HD-ZIPIII TF paralogs CNA and PHB.
• Determine if functional divergence results from distinct gene targets or differential regulation of shared targets.

Main Methods:

• Comparative analysis of gene binding and regulation by CNA and PHB.
• Examination of the role of the START domain in TF-mediated gene regulation.

Main Results:

• CNA and PHB bind to virtually the same set of genes (~99%).
• Both paralogs typically regulate shared target genes in the same direction.
• Functional divergence arises from differential responsiveness of shared binding sites, leading to unique gene regulation.
• The lipid-binding START domain influences the discrimination between responsive and non-responsive binding sites.

Conclusions:

• HD-ZIPIII TF functional divergence is driven by differential usage of shared binding sites, not distinct targets or opposite regulation.
• Paralog-specific transcriptional outcomes are generated from a common network architecture.
• The START domain acts as a key module in mediating this paralog-specific regulation and driving functional divergence.