Jing Wan, Antoinette van Ouwerkerk, Jean-Christophe Mouren, Carla Heredia, Lydie Pradel et al.
There is growing evidence that a wide range of human diseases and physiological traits are influenced by genetic variation of cis-regulatory elements. We and others have shown that a subset of promoter elements, termed Epromoters, also function as enhancer regulators of distal genes. This opens a paradigm in the study of regulatory variants, as single nucleotide polymorphisms (SNPs) within Epromoters might influence the expression of several (distal) genes at the same time, which could disentangle the identification of disease-associated genes. Here, we built a comprehensive resource of human Epromoters using newly generated and publicly available high-throughput reporter assays. We showed that Epromoters display intrinsic and epigenetic features that distinguish them from typical promoters. By integrating Genome-Wide Association Studies (GWAS), expression Quantitative Trait Loci (eQTLs) and 3D chromatin interactions, we found that regulatory variants at Epromoters are concurrently associated with more disease and physiological traits, as compared with typical promoters. To dissect the regulatory impact of Epromoter variants, we evaluated their impact on regulatory activity by analyzing allelic-specific high-throughput reporter assays and provided reliable examples of pleiotropic Epromoters. In summary, our study represents a comprehensive resource of regulatory variants supporting the pleiotropic role of Epromoters.
Jing Wan, Antoinette van Ouwerkerk, Jean-Christophe Mouren, Carla Heredia, Lydie Pradel, Benoit Ballester, Jean-Christophe Andrau, Salvatore Spicuglia. Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits. 2024-12-27. https://doi.org/10.1093/nar/gkae1270
Variant-focused MPRA dataset compiled by Wan et al. from Abell et al. 2022 in GM12878. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Cooper et al. 2022 in HEK293T. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Lu et al. 2021 in Jurkat T cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Long et al. 2022 in Melanoma. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused SuRE-seq dataset compiled by Wan et al. from Arensbergen et al. 2019 in HepG2. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Mouri et al. 2022 in Jurkat T cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Targeted CapSTARR-seq of a human reference-sequence promoter library in RPMI under Basal / Untreated. The table retains promoter elements called Active in every available biological replicate and aggregates their GEO-processed FPKM and fold-change values.
Variant-focused MPRA dataset compiled by Wan et al. from Long et al. 2022 in Melanocyte. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Targeted CapSTARR-seq of a human reference-sequence promoter library in CCRF-CEM under Basal / Untreated. The table retains promoter elements called Active in every available biological replicate and aggregates their GEO-processed FPKM and fold-change values.
Variant-focused MPRA dataset compiled by Wan et al. from Lu et al. 2021 in GM12878. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Lu et al. 2021 in Jurkat T cells IFNa. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Mattioli et al. 2019 in HepG2. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused STARR-seq dataset compiled by Wan et al. from Zhang et al. 2018 in LNCaP cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Choi et al. 2020 in melanoma cell line. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Khetan et al. 2021 in MIN6 β cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Targeted CapSTARR-seq of a human reference-sequence promoter library in GM12878 under Basal / Untreated. The table retains promoter elements called Active in every available biological replicate and aggregates their GEO-processed FPKM and fold-change values.
Targeted CapSTARR-seq of a human reference-sequence promoter library in CCRF-CEM under 100 ng/mL IFN-α for 6h. The table retains promoter elements called Active in every available biological replicate and aggregates their GEO-processed FPKM and fold-change values.
Variant-focused MPRA dataset compiled by Wan et al. from Myint et al. 2019 in SH-SY5Y. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Mattioli et al. 2019 in K562. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Myint et al. 2019 in K562. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused STARR-seq dataset compiled by Wan et al. from Penner-Goeke et al. 2022 in U138MG cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Tewhey et al. 2016 in LCLs. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Ulirsch et al. 2016 in K562. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused STARR-seq dataset compiled by Wan et al. from Liu et al. 2017 in HEK293T. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused STARR-seq dataset compiled by Wan et al. from Penner-Goeke et al. 2022 in U2OS-GR cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused MPRA dataset compiled by Wan et al. from Bourges et al. 2020 in stimulated CD4 T cells. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused SuRE-seq dataset compiled by Wan et al. from Arensbergen et al. 2019 in K562. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Variant-focused STARR-seq dataset compiled by Wan et al. from Kalita et al. 2018 in LCLs-GM18507. The table contains the source study's significant allelic-impact calls with source provenance and Epromoter/GWAS annotations where an rsID match was available.
Original supplemental and deposited inputs retained for this study. Download files individually or together as a ZIP; nested folders are preserved. Source reuse terms apply, and sequencing reads may be omitted.
Download all 17 files (ZIP)geo_GSE268615/filelist.txtgeo_GSE268615/GSE268615.softgeo_GSE268615/GSE268615_family.softgeo_GSE268615/GSM8295411_CapSTARR-seq_RPMI_WT_rep1_VS_input.tsv.gzgeo_GSE268615/GSM8295412_CapSTARR-seq_RPMI_WT_rep2_VS_input.tsv.gzgeo_GSE268615/GSM8295414_CapSTARR-seq_CEM_WT_rep1_VS_input.tsv.gzgeo_GSE268615/GSM8295415_CapSTARR-seq_CEM_WT_rep2_VS_input.tsv.gzgeo_GSE268615/GSM8295416_CapSTARR-seq_CEM_IFNa_rep1_VS_input.tsv.gzgeo_GSE268615/GSM8295417_CapSTARR-seq_CEM_IFNa_rep2_VS_input.tsv.gzgeo_GSE268615/GSM8295419_CapSTARR-seq_GM12878_WT_rep1_VS_input.tsv.gzgeo_GSE268615/GSM8295420_CapSTARR-seq_GM12878_WT_rep2_VS_input.tsv.gzgeo_GSE268615/GSM8295421_CapSTARR-seq_GM12878_WT_rep3_VS_input.tsv.gzgkae1270_supplemental_files.zipsupplemental/Supplemental Table 1_new.xlsxsupplemental/Supplemental Table 3.xlsxsupplemental/Supplemental Table 5.xlsxsupplemental/Supplemental Table 7.xlsx