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Epromoters function as a hub to recruit key transcription factors required for the inflammatory response

Abstract : Gene expression is controlled by the involvement of gene-proximal (promoters) and distal (enhancers) regulatory elements. Our previous results demonstrated that a subset of gene promoters, termed Epromoters, work as bona fide enhancers and regulate distal gene expression. Here, we hypothesized that Epromoters play a key role in the coordination of rapid gene induction during the inflammatory response. Using a high-throughput reporter assay we explored the function of Epromoters in response to type I interferon. We find that clusters of IFNa-induced genes are frequently associated with Epromoters and that these regulatory elements preferentially recruit the STAT1/2 and IRF transcription factors and distally regulate the activation of interferon-response genes. Consistently, we identified and validated the involvement of Epromoter-containing clusters in the regulation of LPS-stimulated macrophages. Our findings suggest that Epromoters function as a local hub recruiting the key TFs required for coordinated regulation of gene clusters during the inflammatory response.
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https://hal-amu.archives-ouvertes.fr/hal-03513051
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Submitted on : Wednesday, January 5, 2022 - 4:27:58 PM
Last modification on : Thursday, January 13, 2022 - 2:34:08 PM
Long-term archiving on: : Wednesday, April 6, 2022 - 9:21:27 PM

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David Santiago-Algarra, Charbel Souaid, Himanshu Singh, Lan Dao, Saadat Hussain, et al.. Epromoters function as a hub to recruit key transcription factors required for the inflammatory response. Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-26861-0⟩. ⟨hal-03513051⟩

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