We identify that signal-dependent and ligand-dependent enhancer activation programs require release of a shared enhancer RNA (eRNA) transcription checkpoint. Further mechanistic evidence reveals signal-dependent activation of P-TEFb on enhancers, which licenses the enhancer transcriptional program by overcoming pausing of transcription and promoting eRNA elongation.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Long, H. K., Prescott, S. L. & Wysocka, J. Ever-changing landscapes: transcriptional enhancers in development and evolution. Cell 167, 1170–1187 (2016). A review article that outlines that enhancers are highly specific to cell types and signals.
Kim, T.-K. & Shiekhattar, R. Architectural and functional commonalities between enhancers and promoters. Cell 162, 948–959 (2015). A review article that presents transcriptional regulatory features at promoters and enhancers.
Chen, F. X., Smith, E. R. & Shilatifard, A. Born to run: control of transcription elongation by RNA polymerase II. Nat. Rev. Mol. Cell Biol. 19, 464–478 (2018). A review article that describes the regulation mechanisms of transcription elongation factors.
Nair, S. J. et al. Transcriptional enhancers at 40: evolution of a viral DNA element to nuclear architectural structures. Trends Genet. 38, 1019–1047 (2022). A review article that presents mechanisms of transcriptional activation of signal-induced enhancers.
Kaya-Okur, H. S. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930 (2019). This paper reports that the CUT&Tag method successfully captures chromatin component enrichment signals.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Wang, L et al. An eRNA transcription checkpoint for diverse signal-dependent enhancer activation programs. Nat. Genet. https://doi.org/10.1038/s41588-025-02138-w (2025).
Rights and permissions
About this article
Cite this article
A conserved checkpoint for ligand-dependent enhancer activation. Nat Genet 57, 782–783 (2025). https://doi.org/10.1038/s41588-025-02146-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41588-025-02146-w
