Gene regulation by convergent promoters
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.
Authors
- Robert Schwarz (ORCID: https://orcid.org/0000-0002-0654-0943)
- Marco Groth (ORCID: https://orcid.org/0000-0002-9199-8990)
- Kanstantsin Siniuk
- Martin Bens (ORCID: https://orcid.org/0000-0001-7940-6668)
- Alexander Loewer (ORCID: https://orcid.org/0000-0002-8819-3040)
- Martin Fischer (ORCID: https://orcid.org/0000-0002-3429-1876)
- Alena van Bömmel (ORCID: https://orcid.org/0000-0002-8434-8586)
- Katjana Schwab (ORCID: https://orcid.org/0000-0002-6916-2900)
- Arne Sahm (ORCID: https://orcid.org/0000-0002-7330-1790)
- Steve Hoffmann (ORCID: https://orcid.org/0000-0002-5239-7201)
- Morgan A. Sammons (ORCID: https://orcid.org/0000-0002-5329-1169)
- Konstantin Riege (ORCID: https://orcid.org/0009-0002-9881-7563)
- Elina Wiechens (ORCID: https://orcid.org/0000-0002-1594-7817)
- Flavia Vigliotti (ORCID: https://orcid.org/0009-0008-6294-9170)
- Ivonne Görlich
Institutions
- Technische Universität Darmstadt (DE)
- University at Albany, State University of New York (US)
- Leibniz Institute of Environmental Medicine (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Ruhr University Bochum (DE)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1038/s41588-024-02025-w
- Citations
- 9
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- Deutsche Forschungsgemeinschaft