A systematic interactome of Saccharomyces cerevisiae SET1C expands its functional landscape and identifies candidate regulatory connections
Abstract
Set1 is the catalytic subunit of SET1C or COMPASS, which methylates histone H3K4 and serves as a scaffold for the association of seven tightly bound polypeptides. We have employed yeast two-hybrid screenings to determine the interactome of Set1 and each subunit, providing a unique resource for exploring known and novel roles of the complex. Our screenings identified a multitude of potential interactors involved in chromatin regulation, DNA replication, meiotic breaks, and Ty transposition, processes previously associated with SET1C. Consistent with Set1 being an RNA-binding protein, the screens link SET1C to multiple aspects of RNA biogenesis, including pre-mRNA splicing and polyadenylation. The results reveal that several importins are candidate interactors of Set1, along with RGG motif-containing proteins, providing insights into the mechanisms by which Set1 moves between cytoplasmic and nuclear compartments. We further reveal that reconstituted SET1C interacts with the AT-hook domain of the chromatin remodeler Snf2 and methylates multiple arginines within this domain. In vivo, we report that the ARTSTRGR AT-hook motif is methylated in a Set1-dependent manner, revealing new interplay between lysine and arginine methylation.
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BibTeX
@article{luciano2026systematic,
title = {{A systematic interactome of Saccharomyces cerevisiae SET1C expands its functional landscape and identifies candidate regulatory connections}},
author = {Pierre Luciano and Kihyun Park and Stephane Audebert and Luc Camoin and Carlos A Niño and Da Kyeong Park and Isabella E Maudlin and Marion Dubarry and Lara Lee and Marlene Oeffinger and Jean D Beggs and Young Hye Kim and Jaehoon Kim and Bernhard Dichtl and Vincent Geli},
journal = {eLife},
year = {2026},
month = sep,
doi = {10.7554/elife.109886},
url = {https://hal.science/hal-05855054v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A systematic interactome of Saccharomyces cerevisiae SET1C expands its functional landscape and identifies candidate regulatory connections
AU - Pierre Luciano
AU - Kihyun Park
AU - Stephane Audebert
AU - Luc Camoin
AU - Carlos A Niño
AU - Da Kyeong Park
AU - Isabella E Maudlin
AU - Marion Dubarry
AU - Lara Lee
AU - Marlene Oeffinger
AU - Jean D Beggs
AU - Young Hye Kim
AU - Jaehoon Kim
AU - Bernhard Dichtl
AU - Vincent Geli
PY - 2026
DA - 2026/09/16
JO - eLife
DO - 10.7554/elife.109886
UR - https://hal.science/hal-05855054v1
AB - Set1 is the catalytic subunit of SET1C or COMPASS, which methylates histone H3K4 and serves as a scaffold for the association of seven tightly bound polypeptides. We have employed yeast two-hybrid screenings to determine the interactome of Set1 and each subunit, providing a unique resource for exploring known and novel roles of the complex. Our screenings identified a multitude of potential interactors involved in chromatin regulation, DNA replication, meiotic breaks, and Ty transposition, processes previously associated with SET1C. Consistent with Set1 being an RNA-binding protein, the screens link SET1C to multiple aspects of RNA biogenesis, including pre-mRNA splicing and polyadenylation. The results reveal that several importins are candidate interactors of Set1, along with RGG motif-containing proteins, providing insights into the mechanisms by which Set1 moves between cytoplasmic and nuclear compartments. We further reveal that reconstituted SET1C interacts with the AT-hook domain of the chromatin remodeler Snf2 and methylates multiple arginines within this domain. In vivo, we report that the ARTSTRGR AT-hook motif is methylated in a Set1-dependent manner, revealing new interplay between lysine and arginine methylation.
SN - 2050-084X
ER -