Studies of DNA methylation from fungi, plants, and animals indicate that gene body methylation is ancient and highly conserved in eukaryotic genomes, but its role has not been clearly defined. It has been postulated that regulation of alternative splicing of transcripts was an original function of DNA methylation, but a direct experimental test of the effect of methylation on alternative slicing at the whole genome level has never been performed. To do this, we developed a unique method to administer RNA interference (RNAi) in a high-throughput and noninvasive manner and then used it to knock down the expression of DNA methyl-transferase 3 (dnmt3), which is required for de novo DNA methylation. We chose the honey bee (Apis mellifera) for this test because it has recently emerged as an important model organism for studying the effects of DNA methylation on development and social behavior, and DNA methylation in honey bees is predominantly on gene bodies. Here we show that dnmt3 RNAi decreased global genomic methylation level as expected and in addition caused widespread and diverse changes in alternative splicing in fat tissue. Four different types of splicing events were affected by dnmt3 gene knockdown, and change in two types, exon skipping and intron retention, was directly related to decreased methylation. These results demonstrate that one function of gene body DNA methylation is to regulate alternative splicing.
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http://dx.doi.org/10.1073/pnas.1310735110 | DOI Listing |
Mar Biotechnol (NY)
January 2025
Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, China.
The influence of sex and heredity on DNA methylation in the somatic tissues of mice has been well-documented, with similar hereditary effects reported in honeybees. However, the extent to which these factors affect DNA methylation in molluscan somatic tissues remains poorly understood. In this study, we investigated genomic DNA methylation patterns in the adductor muscle of two genetically distinct oyster strains using whole-genome bisulfite sequencing (WGBS).
View Article and Find Full Text PDFActa Pharm Sin B
December 2024
Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed -defective NSCLC cells.
View Article and Find Full Text PDFRSC Adv
January 2025
Medicinal Chemistry Department, Faculty of Pharmacy, Minia University 61519 Minia Egypt.
Cancer is one of the leading causes of morbidity and mortality worldwide. One of the primary causes of cancer development and progression is epigenetic dysregulation, which is a heritable modification that alters gene expression without changing the DNA sequence. Therefore, targeting these epigenetic changes has emerged as a promising therapeutic strategy.
View Article and Find Full Text PDFCurr Mol Med
January 2025
Division of Biological and Health Sciences, University of Pittsburgh, 300 Campus Drive, Bradford PA 16701.
Invasive ductal carcinoma (IDC) is the most common type of breast cancer, primarily affecting women in the United States and across the world. This review summarizes key concepts related to IDC causes, treatment approaches, and the identification of biological markers for specific prognoses. Furthermore, we reviewed many studies, including those involving patients with IDC and ductal carcinoma in situ (DCIS) that progressed to IDC.
View Article and Find Full Text PDFCardiovasc Diabetol
January 2025
Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, 29010, Málaga, Spain.
Background: The prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements.
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