Journal Article DKFZ-2024-01772

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

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2024
Elsevier New York, NY

Cell 187(21), 6088-6103.e18 () [10.1016/j.cell.2024.08.011]
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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.

Keyword(s): 5-formylcytosine ; B-box ; RNA Pol III ; TDG ; TET ; Xenopus ; ZGA ; perinucleolar compartment ; tRNA ; tRNA-iMet

Classification:

Note: #LA:A050# / 2024 Oct 17;187(21):6088-6103.e18 / DKFZ-ZMBH Alliance

Contributing Institute(s):
  1. A050 Molekulare Embryologie (A050)
Research Program(s):
  1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024
Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2024-09-04, last modified 2025-08-19


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