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Nat Genet April 1, 2016; 48 (4): 417-26.

Active DNA demethylation at enhancers during the vertebrate phylotypic period.

Bogdanović O , Smits AH , de la Calle Mustienes E , Tena JJ , Ford E , Williams R , Senanayake U , Schultz MD , Hontelez S , van Kruijsbergen I , Rayon T , Gnerlich F , Carell T , Veenstra GJ , Manzanares M , Sauka-Spengler T , Ecker JR , Vermeulen M , Gómez-Skarmeta JL , Lister R .

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.

PubMed ID: 26928226
PMC ID: PMC5912259
Article link: Nat Genet
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: crebbp tet2 tet3
GO keywords: chromatin binding [+]

GEO Series: GSE68087: NCBI

Article Images: [+] show captions
References [+] :
Almeida, 5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development. 2012, Pubmed