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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma

by
Chiemi F. Lynch-Sutherland
1,2,3,
Lorissa I. McDougall
1,
Peter A. Stockwell
1,4,
Aniruddha Chatterjee
1,4,
Teena K. J. B. Gamage
5,6,7,
Joanna L. James
7,
Euan J. Rodger
1,4,
Robert J. Weeks
1,
Jackie L. Ludgate
1,
Erin C. Macaulay
1,† and
Michael R. Eccles
1,4,*,†
1
Department of Pathology and Molecular Medicine, Dunedin School of Medicine, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand
2
Children’s Medical Research Institute, Westmead, NSW 2145, Australia
3
Kids Neuroscience Centre, Kids Research, The Children’s Hospital at Westmead, Westmead, NSW 2145, Australia
4
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Level 2, 3A Symonds Street, Private Bag 92019, Auckland 1010, New Zealand
5
Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand
6
Auckland Bioengineering Institute, The University of Auckland, Auckland 1010, New Zealand
7
Department of Obstetrics, Gynaecology, and Reproductive Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1010, New Zealand
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2026, 27(13), 5827; https://doi.org/10.3390/ijms27135827
Submission received: 15 May 2026 / Revised: 23 June 2026 / Accepted: 25 June 2026 / Published: 27 June 2026
(This article belongs to the Special Issue Melanoma: From Molecular Pathology to Therapeutic Approaches, 2nd Edition)
Versions Notes

Abstract

Transposable elements (TEs) play important roles during development and disease, including through transcriptional activation of TE-associated genes during early human development. Moreover, based on the functional and epigenetic similarities between early development and cancer, TE-associated genes contribute not only to early human development, but frequently contribute to cancer progression. In this study, we hypothesised that recruitment of TE-associated genes during cancer onset occurs through epigenetic regulatory processes, especially involving DNA hypomethylation accompanied by transcriptional upregulation of early developmental pathways, such that, when reactivated inappropriately in later life, they may drive malignancy. It is unknown, however, to what extent DNA methylation changes are critically involved in the transcriptional activation of TE-associated genes. Accordingly, to investigate this we used the RepExpress tool to identify developmentally regulated TE-associated genes in placenta and human embryonic stem cells (hESCs), which we then investigated by targeted deep bisulfite sequencing (TDBS) to determine the methylation status of the identified TE-associated genes in placenta, somatic tissues, and melanoma cell lines. Outcomes suggest that DNA methylation may be one of the regulatory factors underscoring transcriptional activation of TE-associated genes, but that methylation is not necessarily the sole factor involved in regulating the transcriptional activation of TE-associated genes during malignant transformation.
Keywords: transposable elements; endogenous retroviruses; placental-enriched; human-embryonic-stem-cell-enriched; melanoma; TE-associated transcripts transposable elements; endogenous retroviruses; placental-enriched; human-embryonic-stem-cell-enriched; melanoma; TE-associated transcripts

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MDPI and ACS Style

Lynch-Sutherland, C.F.; McDougall, L.I.; Stockwell, P.A.; Chatterjee, A.; Gamage, T.K.J.B.; James, J.L.; Rodger, E.J.; Weeks, R.J.; Ludgate, J.L.; Macaulay, E.C.; et al. Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma. Int. J. Mol. Sci. 2026, 27, 5827. https://doi.org/10.3390/ijms27135827

AMA Style

Lynch-Sutherland CF, McDougall LI, Stockwell PA, Chatterjee A, Gamage TKJB, James JL, Rodger EJ, Weeks RJ, Ludgate JL, Macaulay EC, et al. Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma. International Journal of Molecular Sciences. 2026; 27(13):5827. https://doi.org/10.3390/ijms27135827

Chicago/Turabian Style

Lynch-Sutherland, Chiemi F., Lorissa I. McDougall, Peter A. Stockwell, Aniruddha Chatterjee, Teena K. J. B. Gamage, Joanna L. James, Euan J. Rodger, Robert J. Weeks, Jackie L. Ludgate, Erin C. Macaulay, and et al. 2026. "Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma" International Journal of Molecular Sciences 27, no. 13: 5827. https://doi.org/10.3390/ijms27135827

APA Style

Lynch-Sutherland, C. F., McDougall, L. I., Stockwell, P. A., Chatterjee, A., Gamage, T. K. J. B., James, J. L., Rodger, E. J., Weeks, R. J., Ludgate, J. L., Macaulay, E. C., & Eccles, M. R. (2026). Transcriptional Activation of Transposable Element (TE)-Associated Genes Is Frequently Associated with Altered Promoter Methylation in Placenta and Melanoma. International Journal of Molecular Sciences, 27(13), 5827. https://doi.org/10.3390/ijms27135827

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