PUBLICATION
Active DNA demethylation at enhancers during the vertebrate phylotypic period
- Authors
- Bogdanović, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., van Kruijsbergen, I., Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gómez-Skarmeta, J.L., Lister, R.
- ID
- ZDB-PUB-160302-11
- Date
- 2016
- Source
- Nature Genetics 48(4): 417-26 (Journal)
- Registered Authors
- Gómez-Skarmeta, José Luis, Sauka-Spengler, Tatjana, Tena, Juan
- Keywords
- Embryogenesi,s Epigenetics, Epigenomics
- Datasets
- GEO:GSE68087
- MeSH Terms
-
- Animals
- Body Patterning
- DNA Methylation*
- Enhancer Elements, Genetic*
- Epigenesis, Genetic
- Gene Expression Regulation, Developmental
- Mice
- Xenopus
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 26928226 Full text @ Nat. Genet.
Citation
Bogdanović, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., van Kruijsbergen, I., Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gómez-Skarmeta, J.L., Lister, R. (2016) Active DNA demethylation at enhancers during the vertebrate phylotypic period. Nature Genetics. 48(4):417-26.
Abstract
The vertebrate body plan and organs are shaped during a conserved embryonic phase called the phylotypic stage. However, the mechanisms that guide the epigenome through this transition and their evolutionary conservation remain elusive. Here we report widespread DNA demethylation of enhancers during the phylotypic period in zebrafish, Xenopus tropicalis and mouse. These enhancers are linked to developmental genes that display coordinated transcriptional and epigenomic changes in the diverse vertebrates during embryogenesis. Binding of Tet proteins to (hydroxy)methylated DNA and enrichment of 5-hydroxymethylcytosine in these regions implicated active DNA demethylation in this process. Furthermore, loss of function of Tet1, Tet2 and Tet3 in zebrafish reduced chromatin accessibility and increased methylation levels specifically at these enhancers, indicative of DNA methylation being an upstream regulator of phylotypic enhancer function. Overall, our study highlights a regulatory module associated with the most conserved phase of vertebrate embryogenesis and suggests an ancient developmental role for Tet dioxygenases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping