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Factors with Dual Roles as Activators and Repressors Regulate Intermediate Expression Levels

GSE234559 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/04/06 Platform GPL21273
Summary
Precise control of gene expression levels is essential for normal cell functions, yet how they are defined and tightly maintained, particularly at intermediate levels, remains elusive. Here, using a series of new sequencing, imaging, and functional assays, we uncover a class of transcription factors, referred to as dual TFs, which reduce high expression but increase low expression to achieve stable intermediate levels. Dual TFs directly exert activating and repressing functions via condensate-forming domains that compartmentalize core transcriptional unit selectively. Clinically relevant mutations in these domains, which are linked to a range of developmental disorders, impair condensate selectivity and dual TF activity. These results collectively address a fundamental question in expression regulation and demonstrate the potential of dual TFs as powerful effectors for engineering controlled expression levels.
Published in
Dual-role transcription factors stabilize intermediate expression levels
He J, Huo X, Pei G et al. · Cell 2024 · PMID 38631355 · doi:10.1016/j.cell.2024.03.023
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Also filed as BioProject PRJNA982046 and SRA study SRP441984. Searching any of these in the dataset finder brings you back here.

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