5-formylcytosine is an activating epigenetic mark for Pol III during zygotic reprogramming

Parasyraki, Eleftheria, Mallick, Medhavi, Hatch, Victoria, Vastolo, Viviana, Musheev, Michael U., Karaulanov, Emil, Gopanenko, Alexandr, Moxon, Simon ORCID: https://orcid.org/0000-0003-4644-1816, Méndez-Lago, Maria, Han, Dandan, Schomacher, Lars, Mukherjee, Debasish and Niehrs, Christof (2024) 5-formylcytosine is an activating epigenetic mark for Pol III during zygotic reprogramming. Cell. ISSN 0092-8674

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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 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 regulatory mark to promote TfIIIc and Pol III recruitment, as well as tRNA expression. Concordantly, 5fC modification of a tRNA-iMet transgene enhances its expression in vivo. The results establish 5fC as activating epigenetic mark during zygotic reprogramming of Pol III gene expression.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	LivePure Connector
Date Deposited:	03 Sep 2024 17:33
Last Modified:	02 Oct 2024 10:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/96495
DOI:	10.1016/j.cell.2024.08.011

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