biostudies-literatureLeydon ARHHS | National Institutes of HealthLife Sciences Research FoundationHoward Hughes Medical InstituteNIGMS NIH HHSe2206986119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9564828biostudies-literatureUnknown119(41)The corepressor TOPLESS (TPL) and its paralogs coordinately regulate a large number of genes critical to plant development and immunity. As in many members of the larger pan-eukaryotic Tup1/TLE/Groucho corepressor family, TPL contains a Lis1 Homology domain (LisH), whose function is not well understood. We have previously found that the LisH in TPL-and specifically the N-terminal 18 amino acid alpha-helical region (TPL-H1)-can act as an autonomous repression domain. We hypothesized that homologous domains across diverse LisH-containing proteins could share the same function. To test that hypothesis, we built a library of H1s that broadly sampled the sequence and evolutionary space of LisH domains, and tested their activity in a synthetic transcriptional repression assay in <i>SaccharomycesProceedings of the National Academy of Sciences of the United States of AmericaA single helix repression domain is functional across diverse eukaryotes.PMC9564828NAR01 GM10708410115746Ramos Baez RNemhauser JLLeydon ARfalseA single helix repression domain is functional across diverse eukaryotes.The corepressor TOPLESS (TPL) and its paralogs coordinately regulate a large number of genes critical to plant development and immunity. As in many members of the larger pan-eukaryotic Tup1/TLE/Groucho corepressor family, TPL contains a Lis1 Homology domain (LisH), whose function is not well understood. We have previously found that the LisH in TPL-and specifically the N-terminal 18 amino acid alpha-helical region (TPL-H1)-can act as an autonomous repression domain. We hypothesized that homologous domains across diverse LisH-containing proteins could share the same function. To test that hypothesis, we built a library of H1s that broadly sampled the sequence and evolutionary space of LisH domains, and tested their activity in a synthetic transcriptional repression assay in <i>Saccharomyces2022-01-01T00:00:00Z2022 Oct2026-07-14T19:05:47.861Z2025-04-07T03:20:47.785ZS-EPMC95648283619119210.1073/pnas.2206986119