Wray, G. A. The evolutionary significance of cis-regulatory mutations. Nat. Rev. Genet. 8, 206–216 (2007).
Article CAS PubMed Google Scholar
Wagner, G. P. & Lynch, V. J. The gene regulatory logic of transcription factor evolution. Trends Ecol. Evol. 23, 377–385 (2008).
Vande Zande, P., Hill, M. S. & Wittkopp, P. J. Pleiotropic effects of trans-regulatory mutations on fitness and gene expression. Science 377, 105–109 (2022).
Article CAS PubMed PubMed Central Google Scholar
Sabarís, G., Laiker, I., Preger-Ben Noon, E. & Frankel, N. Actors with multiple roles: pleiotropic enhancers and the paradigm of enhancer modularity. Trends Genet. 35, 423–433 (2019).
Laiker, I. & Frankel, N. Pleiotropic enhancers are ubiquitous regulatory elements in the human genome. Genome Biol. Evol. 14, evac071 (2022).
Article PubMed PubMed Central Google Scholar
Singh, D. & Yi, S. V. Enhancer pleiotropy, gene expression, and the architecture of human enhancer-gene interactions. Mol. Biol. Evol. 38, 3898–3909 (2021).
Article CAS PubMed PubMed Central Google Scholar
Gasperini, M. et al. A genome-wide framework for mapping gene regulation via cellular genetic screens. Cell 176, 377–390.e19 (2019).
Article CAS PubMed PubMed Central Google Scholar
Huang, Y. et al. Two unrelated distal genes activated by a shared enhancer benefit from localizing inside the same small topological domain. Genes Dev. 39, 348–363 (2025).
Article CAS PubMed PubMed Central Google Scholar
Wan, J. et al. Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits. Nucleic Acids Res. 53, gkae1270 (2025).
Article PubMed PubMed Central Google Scholar
Rajderkar, S. et al. Topologically associating domain boundaries are required for normal genome function. Commun. Biol. 6, 435 (2023).
Article CAS PubMed PubMed Central Google Scholar
Halfon, M. S. Studying transcriptional enhancers: the founder fallacy, validation creep, and other biases. Trends Genet. 35, 93–103 (2019).
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