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

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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 RNA Pol III during zygotic reprogramming. Cell, 187 (21). 6088-6103.e18. 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 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.

Item Type: Article
Additional Information: Data and code availability: NGS data have been deposited at GEO and are publicly available as of the date of publication. Accession numbers are listed in the key resources table. This paper also analyzes existing, publicly available data. The accession numbers for the datasets are listed in the key resources table. This paper does not report original code. Any additional information required to re-analyze the data reported in this paper is available from the lead contact upon request. Funding information: Core facilities instruments used in this work are funded by DFG: Stellaris 8 Falcon Confocal DFG Project no. 497669232 and Illumina Nextseq 500 DFG project no. 329045328. This work was funded by the DFG (Ni 286/18-1).
Uncontrolled Keywords: 5-formylcytosine,b-box,rna pol iii,tdg,tet,xenopus,zga,perinucleolar compartment,trna,trna-imet,biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/1300
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 03 Sep 2024 17:33
Last Modified: 11 Nov 2024 13:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/96495
DOI: 10.1016/j.cell.2024.08.011

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