New Insights into LINE-1 and Its Essential Role in Early Embryo Development

A new review from Genes and Diseases sheds light on the pivotal role of LINE-1 elements in preimplantation development and totipotency, revealing their essential contributions to early mammalian embryogenesis. Once considered mere genomic relics, these transposable elements are now recognized as crucial regulators of cellular fate and developmental progression.

LINE-1, a type of retrotransposon, is actively transcribed in the earliest stages of development, marking its presence as soon as the zygote forms. Its dynamic expression correlates with zygotic genome activation (ZGA), a key process in which the embryo transitions from relying on maternal RNA to independently initiating its gene expression. The activation of LINE-1 facilitates the opening of chromatin architecture, allowing essential transcriptional programs to be established. Without proper LINE-1 activity, embryos face developmental arrest, highlighting its indispensable function.

Beyond its role in chromatin remodeling, LINE-1 interacts with epigenetic regulators, including DNA methylation, histone modifications, and RNA methylation, ensuring precise control of gene expression. These interactions help to maintain genome stability, orchestrating the delicate balance between totipotency and differentiation. The suppression and reactivation of LINE-1 are tightly regulated across developmental stages, ensuring the proper progression from a totipotent state to lineage specification.

LINE-1 also plays a key role in stem cell biology, influencing embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Studies show that modulating LINE-1 expression affects stem cell identity, reinforcing its significance in regenerative medicine and cellular reprogramming. The regulation of LINE-1 has further implications in aging and age-related diseases, with evidence suggesting its involvement in genomic instability and cellular senescence.

The review emphasizes the complexity of LINE-1 regulation and its profound impact on embryogenesis, stem cell biology, and aging. Understanding the molecular mechanisms behind LINE-1’s function could pave the way for novel therapeutic strategies in reproductive medicine, regenerative therapies, and age-related disorders.

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Reference
Ru Ma, Nan Xiao, Na Liu, Expression of LINE-1 elements is required for preimplantation development and totipotency, Genes & Diseases, Volume 12, Issue 5, 2025, 101555, https://doi.org/10.1016/j.gendis.2025.101555

Ru Ma, Nan Xiao, Na Liu, Expression of LINE-1 elements is required for preimplantation development and totipotency, Genes & Diseases, Volume 12, Issue 5, 2025, 101555, https://doi.org/10.1016/j.gendis.2025.101555

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Schematic illustration of the dynamic transcription of TEs during murine pre-implantation development. Minor ZGA occurs at the one-cell stage, while major ZGA occurs at the 2-cell stage. MERV-L expression peaks at the 2-cell stage, declining until the blastocyst stage, while LINE-1 element transcription begins post-fertilization, peaks at the 2-cell stage, and persists through initial cell divisions. ZGA, zygotic genome activation; MERV-L, murine endogenous retrovirus type L.. Image link https://ars.els-cdn.com/content/image/1-s2.0-S2352304225000443-gr2_lrg.jpg
The factors regulating the activity of retrotransposons in early embryo development. Highly coordinated molecular mechanisms, including cis- and trans-acting, RNA decay, and epigenetic modifications such as histone modifications, DNA methylation, RNA methylation, etc., keep LINE-1 under tight control. At the same time, LINE-1 also plays a role in early embryonic development and exit from totipotency in various ways.Image link https://ars.els-cdn.com/content/image/1-s2.0-S2352304225000443-gr3_lrg.jpg
Structures and transposition mechanisms of TEs. In the nucleus, LINE-1 ribonucleoproteins, facilitated by ORF2p, initiate transposition by cleaving one DNA strand, creating 3'OH ends, followed by cleavage of both strands to generate complementary sticky ends.Image link: https://ars.els-cdn.com/content/image/1-s2.0-S2352304225000443-gr1_lrg.jpg

24/06/2025 Compuscript Ltd

Regions: Europe, Ireland

Keywords: Health, Medical, People in health research, Science, Life Sciences

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