Home > Publications database > 5-Formylcytosine is an activating epigenetic mark for RNA Pol III during zygotic reprogramming. |
Journal Article | DKFZ-2024-01772 |
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2024
Elsevier
New York, NY
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Please use a persistent id in citations: doi:10.1016/j.cell.2024.08.011
Abstract: 5-Methylcytosine (5mC) is an established epigenetic mark in vertebrate genomic DNA, but whether its oxidation intermediates formed during TET-mediated DNA demethylation possess an instructive role of their own that is also physiologically relevant remains unresolved. Here, we reveal a 5-formylcytosine (5fC) nuclear chromocenter, which transiently forms during zygotic genome activation (ZGA) in Xenopus and mouse embryos. We identify this chromocenter as the perinucleolar compartment, a structure associated with RNA Pol III transcription. In Xenopus embryos, 5fC is highly enriched on Pol III target genes activated at ZGA, notably at oocyte-type tandem arrayed tRNA genes. By manipulating Tet and Tdg enzymes, we show that 5fC is required as a regulatory mark to promote Pol III recruitment as well as tRNA expression. Concordantly, 5fC modification of a tRNA transgene enhances its expression in vivo. The results establish 5fC as an activating epigenetic mark during zygotic reprogramming of Pol III gene expression.
Keyword(s): 5-formylcytosine ; B-box ; RNA Pol III ; TDG ; TET ; Xenopus ; ZGA ; perinucleolar compartment ; tRNA ; tRNA-iMet
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