DNA demethylases TET2 and TET3 play a fundamental role in thymic invariant natural killer T (iNKT) cell differentiation by mediating DNA demethylation of genes encoding for lineage specifying factors. Paradoxically, differential gene expression analysis revealed that significant number of genes were upregulated upon TET2 and TET3 loss in iNKT cells. This unexpected finding could be potentially explained if loss of TET proteins was reducing the expression of proteins that suppress gene expression. In this study, we discover that TET2 and TET3 synergistically regulate expression, by generating 5hmC across the gene body and by impacting chromatin accessibility. As DROSHA is involved in microRNA biogenesis, we proceed to investigate the impact of TET2/3 loss on microRNAs in iNKT cells. We report that among the downregulated microRNAs are members of the Let-7 family that downregulate the expression of the iNKT cell lineage specifying factor PLZF. Our data link TET proteins with microRNA expression and reveal an additional layer of TET mediated regulation of gene expression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312547 | PMC |
| http://dx.doi.org/10.1101/2024.07.31.605991 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic characteristics and virulence of common but overlooked Yersinia intermedia, Y. frederiksenii, and Y. kristensenii in food.
Int J Food Microbiol
January 2025
College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:
Article Synopsis
- Three species of Yersinia (Y. intermedia, Y. frederiksenii, and Y. kristensenii), common foodborne pathogens, were analyzed using genomic data to uncover their potential threat, revealing significant genomic diversity and a noteworthy presence in Europe and Asia.
- Y. intermedia demonstrated a high level of accessory genes, suggesting adaptability and the ability to acquire beneficial traits, while all three species contained various mobile genetic elements including plasmids and insertion sequences.
- Differences in antibiotic resistance genes and virulence gene composition were noted, with Y. kristensenii being the most virulent, containing the most virulence genes, while Y. frederiksenii showed unique pathogenic mechanisms.
New insights into the epidemiology of Streptococcus suis in pig production systems using whole genome sequencing.
Vet Microbiol
January 2025
Department of Animal Science, ETSEA, Universitat de Lleida, Lleida 25198, Spain. Electronic address:
Streptococcus suis (S. suis) is a major pathogen for pigs, causing large economic losses to the swine industry. Moreover, this bacterium has a zoonotic potential, being capable of infecting humans in close contact with pigs or, less frequently, through contact with pork products.
View Article and Find Full Text PDFCpeb1 remodels cell type-specific translational program to promote fear extinction.
Sci Adv
January 2025
Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Protein translation is crucial for fear extinction, a process vital for adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using a Tet-On 3G genetic approach, we achieved precise temporal control over protein translation in the infralimbic medial prefrontal cortex () during fear extinction. In addition, our results reveal that the disruption of cytoplasmic polyadenylation element binding protein 1 (Cpeb1) leads to notable alterations in cell type-specific translational programs, thereby affecting fear extinction.
View Article and Find Full Text PDFVitamin C and MEK Inhibitor PD0325901 Synergistically Promote Oligodendrocytes Generation by Promoting DNA Demethylation.
Molecules
December 2024
State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
DNA methylation and demethylation are key epigenetic events that regulate gene expression and cell fate. DNA demethylation via oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is typically mediated by TET (ten-eleven translocation) enzymes. The 5hmC modification is considered an intermediate state of DNA demethylation; it is particularly prevalent in the brain and is believed to play a role in the development of many cell types in the brain.
View Article and Find Full Text PDFA mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.
Proc Natl Acad Sci U S A
January 2025
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
is one of the three most frequently mutated genes in age-related clonal hematopoiesis (CH), alongside and (. CH can progress to myeloid malignancies including chronic monomyelocytic leukemia (CMML) and is also strongly associated with inflammatory cardiovascular disease and all-cause mortality in humans. DNMT3A and TET2 regulate DNA methylation and demethylation pathways, respectively, and loss-of-function mutations in these genes reduce DNA methylation in heterochromatin, allowing derepression of silenced elements in heterochromatin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!