2. Academic Validation
  3. Gene regulation by convergent promoters

Gene regulation by convergent promoters

  • Nat Genet. 2025 Jan;57(1):206-217. doi: 10.1038/s41588-024-02025-w.
Elina Wiechens 1,  Flavia Vigliotti # 2,  Kanstantsin Siniuk # 1,  Robert Schwarz 1,  Katjana Schwab 1,  Konstantin Riege 1,  Alena van Bömmel 1,  Ivonne Görlich 3,  Martin Bens 3,  Arne Sahm 1 4 5,  Marco Groth 3,  Morgan A Sammons 6,  Alexander Loewer 2,  Steve Hoffmann 7,  Martin Fischer 8
Affiliations

Affiliations

  • 1 Hoffmann Lab, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
  • 2 Department of Biology, Systems Biology of the Stress Response, Technical University of Darmstadt, Darmstadt, Germany.
  • 3 Core Facility Next Generation Sequencing, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
  • 4 Computational Phenomics Group, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany.
  • 5 Computational Phenomics Group, Ruhr University Bochum, Bochum, Germany.
  • 6 Department of Biological Sciences, The RNA Institute, The State University of New York at Albany, Albany, NY, USA.
  • 7 Hoffmann Lab, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany. [email protected].
  • 8 Hoffmann Lab, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany. [email protected].
  • # Contributed equally.
PMID: 39779959 DOI: 10.1038/s41588-024-02025-w
Abstract

Convergent transcription, that is, the collision of sense and antisense transcription, is ubiquitous in mammalian genomes and believed to diminish RNA expression. Recently, antisense transcription downstream of promoters was found to be surprisingly prevalent. However, functional characteristics of affected promoters are poorly investigated. Here we show that convergent transcription marks an unexpected positively co-regulated promoter constellation. By assessing transcriptional dynamic systems, we identified co-regulated constituent promoters connected through a distinct chromatin structure. Within these cis-regulatory domains, transcription factors can regulate both constituting promoters by binding to only one of them. Convergent promoters comprise about a quarter of all active transcript start sites and initiate 5'-overlapping antisense RNAs-an RNA class believed previously to be rare. Visualization of nascent RNA molecules reveals convergent cotranscription at these loci. Together, our results demonstrate that co-regulated convergent promoters substantially expand the cis-regulatory repertoire, reveal limitations of the transcription interference model and call for adjusting the promoter concept.

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