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Face-to-face: The evolution and engineering of the LisH motif in plants

Solano Sanchez, Janet1; Nemhauser, Jennifer1

Published Sep 06, 2026 on Dryad. https://doi.org/10.5061/dryad.73n5tb3cp

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Abstract

Transcriptional repression is a universal regulatory strategy that allows cells to fine-tune gene expression in response to developmental and environmental cues. In eukaryotes, corepressors are non–DNA-binding proteins that bridge transcription factors to repressor complexes. Plants have evolved a distinct repertoire of corepressors, including the LEUNIG/LEUNIG HOMOLOG family, the TOPLESS/TOPLESS-RELATED family, and HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 15. A unifying feature among several plant and metazoan corepressors is the Lis1 Homology (LisH) domain, a short α-helical motif that mediates oligomerization and complex assembly. Here, we review the structure, conservation, and functional diversification of LisH-containing proteins in Arabidopsis, with a focus on how the first helix of the LisH domain provides a tunable interface for protein–protein interactions and intrinsic repression activity. We propose that the LisH domain represents an ancestral scaffold for assembling repression complexes, later co-opted to integrate chromatin remodeling, ubiquitin-mediated degradation, and environmental signaling in plants. Understanding how these modules evolved from shared ancestral architectures provides a conceptual framework for dissecting how eukaryotes diversified the molecular logic of transcriptional repression and offers design principles for engineering precise synthetic control of the transcriptome.