| Literature DB >> 33235224 |
Christopher B Mulholland1, Atsuya Nishiyama2, Joel Ryan1, Ryohei Nakamura3, Merve Yiğit1, Ivo M Glück4, Carina Trummer1, Weihua Qin1, Michael D Bartoschek1, Franziska R Traube5, Edris Parsa5, Enes Ugur1,6, Miha Modic7, Aishwarya Acharya1, Paul Stolz1, Christoph Ziegenhain8, Michael Wierer6, Wolfgang Enard8, Thomas Carell5, Don C Lamb4, Hiroyuki Takeda3, Makoto Nakanishi2, Sebastian Bultmann9, Heinrich Leonhardt10.
Abstract
Genome-wide DNA demethylation is a unique feature of mammalian development and naïve pluripotent stem cells. Here, we describe a recently evolved pathway in which global hypomethylation is achieved by the coupling of active and passive demethylation. TET activity is required, albeit indirectly, for global demethylation, which mostly occurs at sites devoid of TET binding. Instead, TET-mediated active demethylation is locus-specific and necessary for activating a subset of genes, including the naïve pluripotency and germline marker Dppa3 (Stella, Pgc7). DPPA3 in turn drives large-scale passive demethylation by directly binding and displacing UHRF1 from chromatin, thereby inhibiting maintenance DNA methylation. Although unique to mammals, we show that DPPA3 alone is capable of inducing global DNA demethylation in non-mammalian species (Xenopus and medaka) despite their evolutionary divergence from mammals more than 300 million years ago. Our findings suggest that the evolution of Dppa3 facilitated the emergence of global DNA demethylation in mammals.Entities:
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Year: 2020 PMID： 33235224 PMCID： PMC7686362 DOI： 10.1038/s41467-020-19603-1
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919