LINE-1 (L1) is a class of autonomous mobile genetic elements that form somatic mosaicisms in various tissues of the organism. The activity of L1 retrotransposons is strictly controlled by many factors in somatic and germ cells at all stages of ontogenesis. Alteration of L1 activity was noted in a number of diseases: in neuropsychiatric and autoimmune diseases, as well as in various forms of cancer. Altered activity of L1 retrotransposons for some pathologies is associated with epigenetic changes and defects in the genes involved in their repression. This review discusses the molecular genetic mechanisms of the retrotransposition and regulation of the activity of L1 elements. The contribution of various factors controlling the expression and distribution of L1 elements in the genome occurs at all stages of the retrotransposition. The regulation of L1 elements at the transcriptional, post-transcriptional and integration into the genome stages is described in detail. Finally, this review also focuses on the evolutionary aspects of L1 accumulation and their interplay with the host regulation system.
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http://dx.doi.org/10.3390/genes12101562 | DOI Listing |
Front Immunol
January 2025
Department of Hematology and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Immune dysfunction is one of the hallmarks of cancer and plays critical roles in immunotherapy resistance, but there is no serum biomarker that can be used to evaluate immune-dysfunction status of cancer patients. Here, we identified subtype-specific human endogenous retrovirus K102 envelope (HERV-K102-Env) with immunosuppressive activity in circulating blood as a novel serum immunosuppressive biomarker of cancer. We first generated monoclonal antibodies against K102-Env with high sensitivity and specificity, and we developed an ELISA assay to detect serum K102-Env.
View Article and Find Full Text PDFGenes Cells
January 2025
Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, Japan.
The dysfunction of the innate immune system is well-described as a clinical characteristic of COVID-19. While several groups have reported human endogenous retroviruses (ERVs) as enhancing factors of immune reactivity, characterization of the COVID-19-specific ERVs has not yet been sufficiently conducted. Here, we revealed the transcriptome profile of more than 500 ERV subfamilies and innate immune response genes in eight different cohorts of platelet, peripheral blood mononuclear cells (PBMCs), lung, frontal cortex of brain, ventral midbrain, pooled human umbilical vein endothelial cells (pHUVECs), placenta, and cardiac microvascular endothelial cells (HCMEC) from COVID-19 patients (total; n = 124) and normal samples (total; n = 53) using publicly available datasets.
View Article and Find Full Text PDFCurr Environ Health Rep
January 2025
Institute for Society and Genetics, University of California, Boyer Hall, Room 332, 611 Charles E Young Dr E., UCLA, Los Angeles, CA, 90095, USA.
Purpose Of Review: The burgeoning field of environmental epigenetics has revealed the malleability of the epigenome and uncovered numerous instances of its sensitivity to environmental influences; however, pinpointing specific mechanisms that tie together environmental triggers, epigenetic pathways, and organismal responses has proven difficult. This article describes how Caenorhabditis elegans can fill this gap, serving as a useful model for the discovery of molecular epigenetic mechanisms that are conserved in humans.
Recent Findings: Recent results show that environmental stressors such as methylmercury, arsenite, starvation, heat, bacterial infection, and mitochondrial inhibitors can all have profound effects on the epigenome, with some insults showing epigenetic and organismal effects for multiple generations.
J Biol Chem
January 2025
Department of Biological Sciences, Indian Institute of Science Education and Research Berhampur, India. Electronic address:
Long Interspersed Nuclear Element 1 (LINE1/L1) retrotransposons, which comprise 17% of the human genome, typically remain inactive in healthy somatic cells but are reactivated in several cancers. We previously demonstrated that p53 silences L1 transposons in human somatic cells, potentially acting as a tumor-suppressive mechanism. However, the precise molecular mechanisms underlying p53-mediated repression of L1 and its life cycle intermediates remain unclear.
View Article and Find Full Text PDFNat Commun
January 2025
Institute of Virology, University Medical Center, and Faculty of Medicine, Albert-Ludwig-University Freiburg, Freiburg, Germany.
Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication.
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