The Tet family of methylcytosine dioxygenases (Tet1, Tet2, and Tet3) convert 5-methylcytosine to 5-hydroxymethylcytosine. To date, functional overlap among Tet family members has not been examined systematically in the context of embryonic development. To clarify the potential for overlap among Tet enzymes during development, we mutated the zebrafish orthologs of Tet1, Tet2, and Tet3 and examined single-, double-, and triple-mutant genotypes. Here, we identify Tet2 and Tet3 as the major 5-methylcytosine dioxygenases in the zebrafish embryo and uncover a combined requirement for Tet2 and Tet3 in hematopoietic stem cell (HSC) emergence. We demonstrate that Notch signaling in the hemogenic endothelium is regulated by Tet2/3 prior to HSC emergence and show that restoring expression of the downstream gata2b/scl/runx1 transcriptional network can rescue HSCs in tet2/3 double mutant larvae. Our results reveal essential, overlapping functions for tet genes during embryonic development and uncover a requirement for 5hmC in regulating HSC production.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545447 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2015.07.025 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TNF-α-Induced NF-κB Alter the Methylation Status of Some Stemness Genes in HT-29 Human Colon Cancer Cell.
Adv Biomed Res
November 2024
Department of Cellular and Molecular Nutrition, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background: Acquisition of stem-like properties requires overcoming the epigenetic barrier of differentiation and re-expression of several genes involved in stemness and the cell cycle. DNA methylation is the classic epigenetic mechanism for de/differentiation. The writers and erasers of DNA methylation are not site-specific enzymes for altering specific gene methylation.
View Article and Find Full Text PDFtet2 and tet3 regulate cell fate specification and differentiation events during retinal development.
bioRxiv
December 2024
Department of Ophthalmology, The Louis J. Fox Center for Vision Restoration, The McGowan Institute for Regenerative Medicine, The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America.
Tet enzymes are epigenetic modifiers that impact gene expression via 5mC to 5hmC oxidation. Previous work demonstrated the requirement for Tet and 5hmC during zebrafish retinogenesis. mutants possessed defects in the formation of differentiated retinal neurons, but the mechanisms underlying these defects are unknown.
View Article and Find Full Text PDFGlucocorticoid promotes metastasis of colorectal cancer via co-regulation of glucocorticoid receptor and TET2.
Int J Cancer
December 2024
HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), Hangzhou, China.
Glucocorticoids (GCs), commonly used for anti-inflammatory and cancer treatments, have been linked to the promotion of cancer metastasis. Yet, the molecular mechanisms behind this potential remain poorly understood. Clarifying these mechanisms is crucial for a nuanced understanding and potential refinement of GC therapies in the context of cancer treatment.
View Article and Find Full Text PDFConcomitant loss of TET2 and TET3 results in T cell expansion and genomic instability in mice.
Commun Biol
December 2024
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Article Synopsis
- * TET2 mutations are common in blood cancers like T cell lymphomas, but mice lacking TET2 alone don't show increased T cell growth, likely due to other TET proteins compensating for its loss.
- * Research involving mice with both TET2 and TET3 deficiencies revealed that losing these proteins leads to harmful changes in T cells, including genetic instability, aneuploidy, and increased levels of the oncogene Myc.
Vasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes.
Nat Commun
November 2024
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Article Synopsis
- - Tissue nanotransfection (TNT) uses plasmids (Etv2, Foxc2, and Fli1) to enhance the formation of vasculogenic fibroblasts (VF) in ischemic skin of mice, promoting new blood vessel growth.
- - In vitro studies show that human dermal fibroblasts exhibit increased endothelial gene expression upon EFF nanoelectroporation, with a link to higher ten-eleven translocase (TET) expression.
- - The study demonstrates that TET activation is crucial for VF development in diabetic ischemic limbs, facilitating blood flow restoration and improved wound healing, especially since TET levels are usually lower in diabetic conditions.
Want 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!