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Most human genes are associated with promoters embedded in non-methylated, G + C-rich CpG islands (CGIs). Not all CGIs are found at annotated promoters, however, raising the possibility that many serve as promoters for transcripts that do not code for proteins. To test this hypothesis, we searched for novel transcripts in embryonic stem cells (ESCs) that originate within orphan CGIs. Among several candidates, we detected a transcript that included three members of the micro-RNA family: and . Deletion of the CGI prevented expression of the precursor RNA and depleted the included miRNAs. Mice homozygous for this mutation were sub-viable and showed growth and other defects. The results suggest that despite the identity of their seed sequences, members of the miRNA family exert distinct functions that cannot be complemented by other members.
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http://dx.doi.org/10.3390/epigenomes3010007 | DOI Listing |
Blood
July 2025
Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an orphan disease characterized by the proliferation and infiltration of EBV-infected T/natural killer (NK) cells into multiple organs. Although CAEBV is a heterogeneous disease with diverse clinical courses, its pathogenesis remains poorly understood. In this study, we explored the molecular mechanisms underlying CAEBV by performing a comprehensive multi-omics analysis, including genome, transcriptome, epigenome, and single-cell transcriptome and surface proteome analyses, of 65 CAEBV patients.
View Article and Find Full Text PDFBiomolecules
May 2025
Department of Biology, St. Joseph's University, Philadelphia, PA 19131, USA.
A characteristic of triple-negative breast cancer (TNBC) is the epigenetic regulation of tumor suppressor genes, leading to TNBC heterogeneity and treatment resistance in patients. TNBC exhibits high methylation rates, leading to the silencing of numerous tumor suppressor genes. DNA methyltransferase inhibitors (DNMTis) have shown limited clinical efficacy in TNBC treatment.
View Article and Find Full Text PDFGenes Chromosomes Cancer
April 2025
Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany.
Burkitt lymphoma (BL) is an aggressive germinal center B-cell-derived malignancy. Historically, sporadic, endemic, and immunodeficiency-associated variants were distinguished, which differ in the frequency of Epstein-Barr virus (EBV) positivity. Aiming to identify subgroups based on DNA methylation patterns, we here profiled 96 BL cases, 17 BL cell lines, and six EBV-transformed lymphoblastoid cell lines using Illumina BeadChip arrays.
View Article and Find Full Text PDFPediatr Neurol
December 2024
Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:
iScience
October 2024
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.