Uncovering hidden enhancers through unbiased in vivo testing

Chromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental...

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Detalles Bibliográficos
Autores: Mannion, Brandon J., Tran, Stella, Plajzer-Frick, Ingrid, Novak, Catherine S., Afzal, Veena, Akiyama, Jennifer A, Sospedra, Ismael, Barton, Sarah, Beckman, Erik, Garvin, Tyler H., Godfrey, Patrick, Godoy, Janeth, Hunter, Riana D., Kato, Momoe, Kosicki, Michael, Kronshage, Anne N., Lee, Elizabeth A., Meky, Eman M., Pham, Quan T., von Maydell, Kianna, Zhu, Yiwen, López-Ríos, Javier, Dickel, Diane E., Osterwalder, Marco, Visel, Axel, Pennacchio, Len A
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/422564
Acceso en línea:http://hdl.handle.net/10261/422564
https://api.elsevier.com/content/abstract/scopus_id/105012730962
Access Level:acceso abierto
Palabra clave:Epigenomics
Gene regulation
Descripción
Sumario:Chromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental enhancers with tissue-matched chromatin data, 14% (n = 285) lacked canonical enhancer-associated chromatin signatures. To further assess the prevalence of enhancers missed by chromatin profiling approaches, we used a high-throughput transgenic enhancer assay to screen the regulatory landscapes of two key developmental genes at 5 kb resolution, spanning 1.3 Mb of mouse sequence in total. We observed that 23 of 88 (26%) in vivo enhancers discovered by this approach lacked enhancer-associated chromatin signatures in the respective tissue. Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.

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