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Transposable elements (TEs) increasingly emerge as key regulators of development and disease. TE recruitment contributed to placental evolution, with TE-derived genes supporting placental development. 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Eccles 1, *,† and Erin Macaulay 1,†  \nAcademic Editor: Ana Cristina Gonçalves  \nReceived: 10 February 2026  \nRevised: 8 March 2026  \nAccepted: 11 March 2026  \nPublished: 16 March 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Department of Pathology and Molecular Medicine, Dunedin School of Medicine, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand; [clynch-sutherland@cmri.org.au](clynch-sutherland@cmri.org.au) (C.L.-S.); [peter.stockwell@otago.ac.nz](peter.stockwell@otago.ac.nz) (P.S.); [aniruddha.chatterjee@otago.ac.nz](aniruddha.chatterjee@otago.ac.nz) (A.C.); [erin.macaulay@otago.ac.nz](erin.macaulay@otago.ac.nz) (E.M.)  \n2 Children’s Medical Research Institute, Westmead, NSW 2145, Australia  \n3 Kids Neuroscience Centre, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia  \n* [Correspondence: michael.eccles@otago.ac.nz](Correspondence: michael.eccles@otago.ac.nz)[ ](Correspondence: michael.eccles@otago.ac.nz)† These authors contributed equally to this work.  \nAbstract  \nDedifferentiation—the acquisition of an early developmental state—is a hallmark of cancer. However, the underlying mechanisms that lead to cancer-associated dedifferentiation are not fully understood. Transposable elements (TEs) are becoming increasingly recognised as important regulators of development and disease. The recruitment of TE sequences has played an important role in placental evolution, and TE-derived genes play critical roles in placental development. Although important biological differences exist between tumours and the placenta, the placenta shares certain features with tumours, including the capacity to invade surrounding tissue and modulate the maternal immune response. In this regard, TEs have been implicated in cancer development, and are documented to contribute to oncogenesis through multiple different mechanisms. Moreover, cancers reacquire an epigenetic landscape, which is reflective of early development, and which corresponds to increased phenotypic plasticity, including facilitating the activation of early developmental genes. Many cancers can repurpose developmental genes, including TE-associated genes, which may contribute to pathways involved in invasion and metastasis. Determining whether TE activation is a consequence of broader epigenetic reprogramming or actively contributes to dedifferentiation will be important for understanding cancer biology and may facilitate improvements in cancer diagnosis and treatment.  \nKeywords: transposable element; DNA methylation; epigenetic regulation; embryonic development; cancer  \n1. Introduction: Transposable Elements and Epigenetic Regulation  \nHuman development is an intricately regulated process that has evolved over millions of years. Epigenetic regulation is central to development, shaping the landscape that guidesan individual totipotent cell to divide, eventually becoming a complete organism composed of diverse, specialised cell types contributing to an organism’s function. Precise spatial and temporal regulation of genes and pathways is essential for healthy development and for directing cell fate specification. As a result, each cell type has a unique epigenetic profile that drives its characteristic gene expression pattern, which gives rise to its phenotype and function.  \nTransposable elements (TEs) are repetitive DNA sequences that occupy a substantial proportion of mammalian genomes and comprise multiple classes, including DNA transposons, long-terminal repeat (LTR) retrotransposons, and non-LTR retrotransposons such as long interspersed nuclear elements (LINEs) and short intersper","cbCaiobOCnr3yKZd","https://ap.wps.com/l/cbCaiobOCnr3yKZd","pdf",922477,"English","# Abstract\n# 1. Introduction: Transposable Elements and Epigenetic Regulation\n# 2. Transposable Elements in the Human Genome","[{\"question\":\"Why is dedifferentiation important in cancer?\",\"answer\":\"Dedifferentiation involves acquiring an early developmental state and is a hallmark of cancer. However, the mechanisms leading to cancer-associated dedifferentiation are not fully understood.\"},{\"question\":\"How do transposable elements relate to development and disease?\",\"answer\":\"Transposable elements are repetitive DNA sequences with regulatory roles in development and disease. TE reactivation and expression are frequently observed in cancer tissues.\"},{\"question\":\"What views does the review summarize about how TEs contribute to development and disease?\",\"answer\":\"The review summarizes three viewpoints: TEs as passive passengers with limited contributions, TEs as developmentally selected regulatory modules essential during foetal/placental development, and TEs as active epigenetic drivers of dedifferentiation that can contribute to ageing and aggressive cancer phenotypes.\"}]","Epigenetic Deregulation of Transposable Elements - Epigenetic Regulation and Cancer Processes | PDF",1790086846]