Structural evolution of LEAFY reveals DNA-mediated cooperativity and dimerization shifts at the water-to-land transition
Abstract
The evolution of transcription factor (TF) DNA-binding specificity is a major driver of gene regulatory innovation. Unlike most TFs, which diversify through gene duplication and neofunctionalization, the plant-specific LEAFY (LFY) TF evolved novel binding specificities without extensive duplication. Here, we combine experimental structural determination and biochemical assays to reveal how LFY's dimerization and DNA-binding preferences shifted during the water-to-land transition. We present crystal structures of the LFY DNA-binding domain (DBD) from the hornwort Nothoceros aenigmaticus and the alga Interfilum paradoxum bound to DNA, demonstrating two distinct dimerization mechanisms: one mediated by direct protein-protein interactions and another driven by DNA-mediated cooperativity. In the ancestral state, LFY likely bound DNA as a dimer through DNA-mediated cooperativity, with protein-protein dimerization emerging later, enforcing new DNA-binding preferences. Our findings support a revised evolutionary scenario for LFY, highlighting the dynamic interplay between protein-DNA and protein-protein interactions as key drivers of TF binding specificity. This work deepens our understanding of how structural adaptations in TFs underpin evolutionary transitions in gene regulation.
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BibTeX
@article{verhage2026structural,
title = {{Structural evolution of LEAFY reveals DNA-mediated cooperativity and dimerization shifts at the water-to-land transition}},
author = {Leonie Verhage and Emmanuel Thévenon and Hicham Chahtane and Alice Jegou and Loïc Grandvuillemin and Max H Nanao and Renaud Dumas and Chloe Zubieta and François Parcy},
journal = {Molecular Plant},
year = {2026},
month = sep,
doi = {10.1016/j.molp.2026.09.009},
url = {https://cnrs.hal.science/hal-05805065v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Structural evolution of LEAFY reveals DNA-mediated cooperativity and dimerization shifts at the water-to-land transition
AU - Leonie Verhage
AU - Emmanuel Thévenon
AU - Hicham Chahtane
AU - Alice Jegou
AU - Loïc Grandvuillemin
AU - Max H Nanao
AU - Renaud Dumas
AU - Chloe Zubieta
AU - François Parcy
PY - 2026
DA - 2026/09/23
JO - Molecular Plant
DO - 10.1016/j.molp.2026.09.009
UR - https://cnrs.hal.science/hal-05805065v1
AB - The evolution of transcription factor (TF) DNA-binding specificity is a major driver of gene regulatory innovation. Unlike most TFs, which diversify through gene duplication and neofunctionalization, the plant-specific LEAFY (LFY) TF evolved novel binding specificities without extensive duplication. Here, we combine experimental structural determination and biochemical assays to reveal how LFY's dimerization and DNA-binding preferences shifted during the water-to-land transition. We present crystal structures of the LFY DNA-binding domain (DBD) from the hornwort Nothoceros aenigmaticus and the alga Interfilum paradoxum bound to DNA, demonstrating two distinct dimerization mechanisms: one mediated by direct protein-protein interactions and another driven by DNA-mediated cooperativity. In the ancestral state, LFY likely bound DNA as a dimer through DNA-mediated cooperativity, with protein-protein dimerization emerging later, enforcing new DNA-binding preferences. Our findings support a revised evolutionary scenario for LFY, highlighting the dynamic interplay between protein-DNA and protein-protein interactions as key drivers of TF binding specificity. This work deepens our understanding of how structural adaptations in TFs underpin evolutionary transitions in gene regulation.
SN - 1674-2052
SN - 1752-9867
ER -