A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin.

Charlotte Soneson, Merle Skribbe, Michael B Stadler, Michaela Schwaiger, Vishnu N Suma Sreechakram, Vytautas Iesmantavicius, Daniel Hess, Eliza Pandini Figueiredo Moreno, Sigurd Braun, Jan Seebacher, Sebastien A Smallwood, Marc Bühler

Journal: Molecular cell 2025;85(7):1426-1444.e8

PMID: 40015273

Free Full Text on Elsevier Science View on PubMed

Abstract

Transcription factors (TFs) are key regulators of gene expression, yet many of their targets and modes of action remain unknown. In Schizosaccharomyces pombe, one-third of TFs are solely homology predicted, with few experimentally validated. We created a comprehensive library of 89 endogenously tagged S. pombe TFs, mapping their protein and chromatin interactions using immunoprecipitation-mass spectrometry and chromatin immunoprecipitation sequencing. Our study identified protein interactors for half the TFs, with over a quarter potentially forming stable complexes. We discovered DNA-binding sites for most TFs across 2,027 unique genomic regions, revealing motifs for 38 TFs and uncovering a complex network of extensive TF cross- and autoregulation. Characterization of the largest TF family revealed conserved DNA sequence preferences but diverse binding patterns and identified a repressive heterodimer, Ntu1/Ntu2, linked to perinuclear gene localization. Our TFexplorer webtool makes all data interactively accessible, offering insights into TF interactions and regulatory mechanisms with broad biological relevance.

Address: Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, Switzerland; University of Basel, Petersplatz 10, Basel, Switzerland. Electronic address: [email protected].; Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland.; Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, Switzerland; University of Basel, Petersplatz 10, Basel, Switzerland; SIB Swiss Institute of Bioinformatics, Basel, Switzerland.; Institute for Genetics, Justus-Liebig-University Giessen, Giessen, Germany.; Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, Switzerland.; Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel, Switzerland; University of Basel, Petersplatz 10, Basel, Switzerland. Electronic address: [email protected].

DOI: 10.1016/j.molcel.2025.01.032