{"id":235404,"date":"2025-07-03T18:31:22","date_gmt":"2025-07-03T18:31:22","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/235404\/"},"modified":"2025-07-03T18:31:22","modified_gmt":"2025-07-03T18:31:22","slug":"range-extender-mediates-long-distance-enhancer-activity","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/235404\/","title":{"rendered":"Range extender mediates long-distance enhancer activity"},"content":{"rendered":"
  • \n

    Bower, G. & Kvon, E. Z. Genetic factors mediating long-range enhancer-promoter communication in mammalian development. Curr. Opin. Genet. Dev. 90<\/b>, 102282 (2024).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lettice, L. A. et al. Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly. Proc. Natl Acad. Sci. USA 99<\/b>, 7548\u20137553 (2002).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Serebreni, L. & Stark, A. Insights into gene regulation: from regulatory genomic elements to DNA-protein and protein-protein interactions. Curr. Opin. Cell Biol. 70<\/b>, 58\u201366 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Spitz, F. & Furlong, E. E. M. Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13<\/b>, 613\u2013626 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Field, A. & Adelman, K. Evaluating enhancer function and transcription. Annu. Rev. Biochem. 89<\/b>, 212\u2013234 (2020).<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kim, S. & Wysocka, J. Deciphering the multi-scale, quantitative cis-regulatory code. Mol. Cell 83<\/b>, 373\u2013392 (2023).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nair, S. J. et al. Transcriptional enhancers at 40: evolution of a viral DNA element to nuclear architectural structures. Trends Genet. 38<\/b>, 1019\u20131047 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Long, H. K. et al. Loss of extreme long-range enhancers in human neural crest drives a craniofacial disorder. Cell Stem Cell 27<\/b>, 765\u2013783 (2020).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Padhi, E. M. et al. Coding and noncoding variants in EBF3 are involved in HADDS and simplex autism. Hum. Genomics 15<\/b>, 44 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Yanchus, C. et al. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science 378<\/b>, 68\u201378 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lupi\u00e1\u00f1ez, D. G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161<\/b>, 1012\u20131025 (2015).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Northcott, P. A. et al. Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511<\/b>, 428\u2013434 (2014).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zaugg, J. B. et al. Current challenges in understanding the role of enhancers in disease. Nat. Struct. Mol. Biol. 29<\/b>, 1148\u20131158 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Weischenfeldt, J. & Ibrahim, D. M. When 3D genome changes cause disease: the impact of structural variations in congenital disease and cancer. Curr. Opin. Genet. Dev. 80<\/b>, 102048 (2023).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hafner, A. & Boettiger, A. The spatial organization of transcriptional control. Nat. Rev. Genet. 24<\/b>, 53\u201368 (2023).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Robson, M. I., Ringel, A. R. & Mundlos, S. Regulatory landscaping: how enhancer-promoter communication is sculpted in 3D. Mol. Cell 74<\/b>, 1110\u20131122 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schoenfelder, S. & Fraser, P. Long-range enhancer\u2013promoter contacts in gene expression control. Nat. Rev. Genet. 20<\/b>, 437\u2013455 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485<\/b>, 376\u2013380 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485<\/b>, 381\u2013385 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Oudelaar, A. M. & Higgs, D. R. The relationship between genome structure and function. Nat. Rev. Genet. 22<\/b>, 154\u2013168 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hsieh, T.-H. S. et al. Enhancer\u2013promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1. Nat. Genet. 54<\/b>, 1919\u20131932 (2022).<\/p>\n<\/li>\n

  • \n

    Schwarzer, W. et al. Two independent modes of chromatin organization revealed by cohesin removal. Nature 551<\/b>, 51\u201356 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nora, E. P. et al. Targeted degradation of CTCf decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169<\/b>, 930\u2013944 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171<\/b>, 305\u2013320 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Wutz, G. et al. Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO J. 36<\/b>, 3573\u20133599 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ghavi-Helm, Y. et al. Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nat. Genet. 51<\/b>, 1272\u20131282 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Williamson, I. et al. Developmentally regulated Shh expression is robust to TAD perturbations. Development 146<\/b>, dev179523 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Paliou, C. et al. Preformed chromatin topology assists transcriptional robustness of Shh during limb development. Proc. Natl Acad. Sci. USA 116<\/b>, 12390\u201312399 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Despang, A. et al. Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture. Nat. Genet. 51<\/b>, 1263\u20131271 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Ushiki, A. et al. Deletion of CTCF sites in the SHH locus alters enhancer-promoter interactions and leads to acheiropodia. Nat. Commun. 12<\/b>, 2282 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rodr\u00edguez-Carballo, E. et al. The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes. Genes Dev. 31<\/b>, 2264\u20132281 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Furlong, E. E. M. & Levine, M. Developmental enhancers and chromosome topology. Science 361<\/b>, 1341\u20131345 (2018).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Sagai, T., Hosoya, M., Mizushina, Y., Tamura, M. & Shiroishi, T. Elimination of a long-range cis-regulatory module causes complete loss of limb-specific Shh expression and truncation of the mouse limb. Development 132<\/b>, 797\u2013803 (2005).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Martin, D. I. & Whitelaw, E. The vagaries of variegating transgenes. Bioessays 18<\/b>, 919\u2013923 (1996).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Haruyama, N., Cho, A. & Kulkarni, A. B. Overview: engineering transgenic constructs and mice. Curr. Protoc. Cell Biol. 42<\/b>, 19.10.1\u201319.10.9 (2009).<\/p>\n

    Article<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zabidi, M. A. et al. Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature 518<\/b>, 556\u2013559 (2015).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Butler, J. E. & Kadonaga, J. T. Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs. Genes Dev. 15<\/b>, 2515\u20132519 (2001).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Snetkova, V. et al. Ultraconserved enhancer function does not require perfect sequence conservation. Nat. Genet. 53<\/b>, 521\u2013528 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Osterwalder, M. et al. Characterization of mammalian in vivo enhancers using mouse transgenesis and CRISPR genome editing. Methods Mol. Biol. 2403<\/b>, 147\u2013186 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kvon, E. Z. et al. Comprehensive in vivo interrogation reveals phenotypic impact of human enhancer variants. Cell 180<\/b>, 1262\u20131271 (2020).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lettice, L. A. et al. A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 12<\/b>, 1725\u20131735 (2003).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lettice, L. A., Hill, A. E., Devenney, P. S. & Hill, R. E. Point mutations in a distant sonic hedgehog cis-regulator generate a variable regulatory output responsible for preaxial polydactyly. Hum. Mol. Genet. 17<\/b>, 978\u2013985 (2008).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kosicki, M. et al. VISTA Enhancer browser: an updated database of tissue-specific developmental enhancers. Nucleic Acids Res. https:\/\/doi.org\/10.1093\/nar\/gkae940<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Hollingsworth, E. W. et al. Rapid and quantitative functional interrogation of human enhancer variant activity in live mice. Nat. Commun. 16<\/b>, 409 (2025).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lettice, L. A. et al. Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly. Dev. Cell 22<\/b>, 459\u2013467 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rinzema, N. J. et al. Building regulatory landscapes reveals that an enhancer can recruit cohesin to create contact domains, engage CTCF sites and activate distant genes. Nat. Struct. Mol. Biol. 29<\/b>, 563\u2013574 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zuin, J. et al. Nonlinear control of transcription through enhancer-promoter interactions. Nature 604<\/b>, 571\u2013577 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dillon, N., Trimborn, T., Strouboulis, J., Fraser, P. & Grosveld, F. The effect of distance on long-range chromatin interactions. Mol. Cell 1<\/b>, 131\u2013139 (1997).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Calhoun, V. C., Stathopoulos, A. & Levine, M. Promoter-proximal tethering elements regulate enhancer-promoter specificity in the Drosophila antennapedia complex. Proc. Natl Acad. Sci. USA 99<\/b>, 9243\u20139247 (2002).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Calhoun, V. C. & Levine, M. Long-range enhancer\u2013promoter interactions in the Scr-Antp interval of the Drosophila antennapedia complex. Proc. Natl Acad. Sci. USA 100<\/b>, 9878\u20139883 (2003).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Levo, M. et al. Transcriptional coupling of distant regulatory genes in living embryos. Nature 605<\/b>, 754\u2013760 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Swanson, C. I., Evans, N. C. & Barolo, S. Structural rules and complex regulatory circuitry constrain expression of a notch- and EGFR-regulated eye enhancer. Dev. Cell 18<\/b>, 359\u2013370 (2010).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kubo, N. et al. Promoter-proximal CTCF binding promotes distal enhancer-dependent gene activation. Nat. Struct. Mol. Biol. 28<\/b>, 152\u2013161 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kang, J., Kim, Y. W., Park, S., Kang, Y. & Kim, A. Multiple CTCF sites cooperate with each other to maintain a TAD for enhancer-promoter interaction in the \u03b2-globin locus. FASEB J. 35<\/b>, e21768 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Oh, S. et al. Enhancer release and retargeting activates disease-susceptibility genes. Nature 595<\/b>, 735\u2013740 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Hirsch, N. et al. HDAC9 structural variants disrupting TWIST1 transcriptional regulation lead to craniofacial and limb malformations. Genome Res. 32<\/b>, 1242\u20131253 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, L.-F. et al. Structural elements promote architectural stripe formation and facilitate ultra-long-range gene regulation at a human disease locus. Mol. Cell 83<\/b>, 1446\u20131461 (2023).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pachano, T. et al. Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness. Nat. Genet. 53<\/b>, 1036\u20131049 (2021).<\/p>\n<\/li>\n

  • \n

    Brosh, R. et al. Synthetic regulatory genomics uncovers enhancer context dependence at the Sox2 locus. Mol. Cell https:\/\/doi.org\/10.1016\/j.molcel.2023.02.027<\/a> (2023).<\/p>\n<\/li>\n

  • \n

    Blayney, J. W. et al. Super-enhancers include classical enhancers and facilitators to fully activate gene expression. Cell 186, 5826\u20135839 (2023).<\/p>\n<\/li>\n

  • \n

    Tzchori, I. et al. LIM homeobox transcription factors integrate signaling events that control three-dimensional limb patterning and growth. Development 136<\/b>, 1375\u20131385 (2009).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Watson, B. A. et al. LHX2 mediates the FGF-to-SHH regulatory loop during limb development. J. Dev. Biol. 6<\/b>, 13 (2018).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Liu, G. & Dean, A. Enhancer long-range contacts: the multi-adaptor protein LDB1 is the tie that binds. Biochim. Biophys. Acta 1862<\/b>, 625\u2013633 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Monahan, K., Horta, A. & Lomvardas, S. LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice. Nature 565<\/b>, 448\u2013453 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Krivega, I., Dale, R. K. & Dean, A. Role of LDB1 in the transition from chromatin looping to transcription activation. Genes Dev. 28<\/b>, 1278\u20131290 (2014).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Deng, W. et al. Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149<\/b>, 1233\u20131244 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chandrashekar, H. et al. A multi-looping chromatin signature predicts dysregulated gene expression in neurons with familial Alzheimer\u2019s disease mutations. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2024.02.27.582395<\/a> (2024).<\/p>\n<\/li>\n

  • \n

    Aboreden, N. G. et al. LDB1 establishes multi-enhancer networks to regulate gene expression. Mol. Cell 85<\/b>, 376\u2013393 (2025).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lex, R. K. et al. GLI transcriptional repression regulates tissue-specific enhancer activity in response to Hedgehog signaling. eLife 9<\/b>, e50670 (2020).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Lettice, L. A., Devenney, P., Angelis, C. D. & Hill, R. E. The conserved sonic hedgehog limb enhancer consists of discrete functional elements that regulate precise spatial expression. Cell Rep. 20<\/b>, 1396\u20131408 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Chen, Z. et al. Increased enhancer-promoter interactions during developmental enhancer activation in mammals. Nat. Genet. 56<\/b>, 675\u2013685 (2024).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kvon, E. Z. et al. Progressive loss of function in a limb enhancer during snake evolution. Cell 167<\/b>, 633\u2013642 (2016).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Dickel, D. E., Visel, A. & Pennacchio, L. A. Functional anatomy of distant-acting mammalian enhancers. Philos. Trans. R. Soc. Lond. B 368<\/b>, 20120359 (2013).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Osterwalder, M. et al. HAND2 targets define a network of transcriptional regulators that compartmentalize the early limb bud mesenchyme. Dev. Cell 31<\/b>, 345\u2013357 (2014).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Kothary, R. et al. Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice. Development 105<\/b>, 707\u2013714 (1989).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Pennacchio, L. A. et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature 444<\/b>, 499\u2013502 (2006).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Rigueur, D. & Lyons, K. M. Whole-mount skeletal staining. Methods Mol. Biol. 1130<\/b>, 113\u2013121 (2014).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10<\/b>, 1213\u20131218 (2013).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Buenrostro, J. D., Wu, B., Chang, H. Y. & Greenleaf, W. J. ATAC\u2010seq: a method for assaying chromatin accessibility genome\u2010wide. Curr. Protoc. Mol. Biol. 109<\/b>, 21.29.1\u201321.29.9 (2015).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14<\/b>, 959\u2013962 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26<\/b>, 841\u2013842 (2010).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Satpathy, A. T. et al. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat. Biotechnol. 37<\/b>, 925\u2013936 (2019).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Stuart, T., Srivastava, A., Madad, S., Lareau, C. A. & Satija, R. Single-cell chromatin state analysis with Signac. Nat. Methods 18<\/b>, 1333\u20131341 (2021).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Zhang, Y. et al. Model-based Analysis of ChIP-Seq (MACS). Genome Biol. 9<\/b>, R137 (2008).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Desanlis, I., Paul, R. & Kmita, M. Transcriptional trajectories in mouse limb buds reveal the transition from anterior-posterior to proximal-distal patterning at early limb bud stage. J. Dev. Biol. 8<\/b>, 31 (2020).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Shimizu, H. et al. The AERO system: a 3D-like approach for recording gene expression patterns in the whole mouse embryo. PLoS ONE 8<\/b>, e75754 (2013).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Groza, T. et al. The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease. Nucleic Acids Res. 51<\/b>, D1038\u2013D1045 (2023).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Nishinakamura, R. et al. Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128<\/b>, 3105\u20133115 (2001).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Monti, R. et al. Limb-Enhancer Genie: an accessible resource of accurate enhancer predictions in the developing limb. PLoS Comput. Biol. 13<\/b>, e1005720 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38<\/b>, 576\u2013589 (2010).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Castro-Mondragon, J. A. et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 50<\/b>, D165\u2013D173 (2022).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Puigdevall, P. & Castelo, R. GenomicScores: seamless access to genomewide position-specific scores from R and Bioconductor. Bioinformatics 34<\/b>, 3208\u20133210 (2018).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Karolchik, D. et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 32<\/b>, D493\u2013D496 (2004).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Grant, C. E., Bailey, T. L. & Noble, W. S. FIMO: scanning for occurrences of a given motif. Bioinformatics 27<\/b>, 1017\u20131018 (2011).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9<\/b>, 676\u2013682 (2012).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Jiang, Y. et al. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nat. Genet. 49<\/b>, 1239\u20131250 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n

  • \n

    Andrey, G. et al. Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding. Genome Res. 27<\/b>, 223\u2013233 (2017).<\/p>\n

    Article<\/a>\u00a0
    \n     CAS<\/a>\u00a0
    \n     PubMed<\/a>\u00a0
    \n     PubMed Central<\/a>\u00a0
    \n
    \n Google Scholar<\/a>\u00a0\n <\/p>\n<\/li>\n","protected":false},"excerpt":{"rendered":"Bower, G. & Kvon, E. Z. Genetic factors mediating long-range enhancer-promoter communication in mammalian development. Curr. Opin. Genet.…\n","protected":false},"author":2,"featured_media":235405,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[12495,19803,267,3965,3966,70,16,15],"class_list":{"0":"post-235404","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-development","9":"tag-gene-regulation","10":"tag-genetics","11":"tag-humanities-and-social-sciences","12":"tag-multidisciplinary","13":"tag-science","14":"tag-uk","15":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114790737084296792","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/235404","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=235404"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/235404\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/235405"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=235404"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=235404"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=235404"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}