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Página principal > Artículos > Artículos publicados > The PENGUIN approach to reconstruct protein interactions at enhancer-promoter regions and its application to prostate cancer |
Fecha: | 2023 |
Resumen: | We introduce Promoter-Enhancer-Guided Interaction Networks (PENGUIN), a method for studying protein-protein interaction (PPI) networks within enhancer-promoter interactions. PENGUIN integrates H3K27ac-HiChIP data with tissue-specific PPIs to define enhancer-promoter PPI networks (EPINs). We validated PENGUIN using cancer (LNCaP) and benign (LHSAR) prostate cell lines. Our analysis detected EPIN clusters enriched with the architectural protein CTCF, a regulator of enhancer-promoter interactions. CTCF presence was coupled with the prevalence of prostate cancer (PrCa) single nucleotide polymorphisms (SNPs) within the same EPIN clusters, suggesting functional implications in PrCa. Within the EPINs displaying enrichments in both CTCF and PrCa SNPs, we also show enrichment in oncogenes. We substantiated our identified SNPs through CRISPR/Cas9 knockout and RNAi screens experiments. Here we show that PENGUIN provides insights into the intricate interplay between enhancer-promoter interactions and PPI networks, which are crucial for identifying key genes and potential intervention targets. A dedicated server is available at https://penguin. life. bsc. es/. |
Ayudas: | European Commission 251555 European Commission. Horizon 2020 779282 European Commission. Horizon 2020 727658 European Commission. Horizon 2020 825080 European Commission 754490 European Commission 855923 European Commission 309545 Generalitat de Catalunya SLD040/20/000001 Ministerio de Ciencia, Innovación y Universidades SEV-2015-628 0493-18-2 Ministerio de Ciencia, Innovación y Universidades PRE2018-083662 |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Animals ; Enhancer Elements, Genetic ; Humans ; Male ; Promoter Regions, Genetic ; Prostatic Neoplasms ; Proteins ; Spheniscidae |
Publicado en: | Nature communications, Vol. 14 Núm. 1 (december 2023) , p. 8084, ISSN 2041-1723 |
17 p, 3.1 MB |