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The review discusses the mechanisms of monoallelic expression, such as genomic imprinting, in which gene transcription depends on the parental origin of the allele, and random monoallelic transcription. Data on the regulation of gene activity in the imprinted regions are summarized with a particular focus on the areas controlling imprinting and factors influencing the variability of the imprintome. The prospects of studies of the monoallelic expression are discussed.
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http://dx.doi.org/10.1134/S000629792401005X | DOI Listing |
Nucleic Acids Res
September 2025
Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.
The mammary gland, which primarily develops postnatally, undergoes significant changes during pregnancy and lactation to facilitate milk production. Through the generation and analysis of 480 transcriptomes, we provide the most detailed allelic expression map of the mammary gland, cataloguing cell-type-specific expression from ex-vivo purified cell populations over 10 developmental stages, enabling comparative analysis. The work identifies genes involved in the mammary gland cycle, parental-origin-specific and genetic background-specific expression at cellular and temporal resolution, genes associated with human lactation disorders and breast cancer.
View Article and Find Full Text PDFJ Biol Chem
September 2025
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.
Aminoacyl-tRNA synthetases (aaRSs) catalyze the aminoacylation of tRNA with their cognate amino acids, an essential step in protein biosynthesis. While biallelic mutations in aaRSs often result in severe multi-organ dysfunction accompanied by developmental delays, monoallelic mutations typically cause milder, tissue-specific symptoms. However, a de novo monoallelic nonsense mutation (R534*) in the asparaginyl-tRNA synthetase (AsnRS)-resulting in a premature stop codon and 15-residue C-terminal truncation-has been identified in multiple families and is associated with severe neurodevelopmental symptoms.
View Article and Find Full Text PDFDiverse epigenetic regulatory mechanisms ensure and regulate cellular diversity. Among others, the histone 3 lysine 9 me3 (H3K9me3) post translational modification participates in silencing lineage-inappropriate genes. H3K9me3 restricts access of transcription factors and other regulatory proteins to cell-fate controlled genes.
View Article and Find Full Text PDFAutosomal monoallelic gene expression and asynchronous replication between alleles are well-established features of imprinted genes and genes regulated by allelic exclusion. Inactivation/Stability Centers (I/SCs) are recently described autosomal loci that exhibit epigenetic regulation of allelic expression and replication timing, with differences that can be comparable to those observed between the active and inactive X chromosomes . Here we characterize hundreds of autosomal loci with allele-specific epigenetic regulation of replication timing and gene expression, defining them as I/SCs.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
The RNA-binding protein TRIM71 is essential for brain development, and recent genetic studies in humans have identified as a risk gene for congenital hydrocephal-us (CH). Here, we show that monoallelic missense mutations in are associated with hearing loss (HL) and inner ear aplasia in humans. Utilizing conditional knockout mice carrying a CH and HL-associated mutation, we demonstrate that loss of TRIM71 function during early otic development (embryonic day 9 to 10) causes severe HL.
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