TY  - JOUR
AU  - Parasyraki, Eleftheria
AU  - Mallick, Medhavi
AU  - Hatch, Victoria
AU  - Vastolo, Viviana
AU  - Musheev, Michael U
AU  - Karaulanov, Emil
AU  - Gopanenko, Alexandr
AU  - Moxon, Simon
AU  - Méndez-Lago, Maria
AU  - Han, Dandan
AU  - Schomacher, Lars
AU  - Mukherjee, Debasish
AU  - Niehrs, Christof
TI  - 5-Formylcytosine is an activating epigenetic mark for RNA Pol III during zygotic reprogramming.
JO  - Cell
VL  - 187
IS  - 21
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-01772
SP  - 6088-6103.e18
PY  - 2024
N1  - #LA:A050# / 2024 Oct 17;187(21):6088-6103.e18 / DKFZ-ZMBH Alliance
AB  - 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.
KW  - 5-formylcytosine (Other)
KW  - B-box (Other)
KW  - RNA Pol III (Other)
KW  - TDG (Other)
KW  - TET (Other)
KW  - Xenopus (Other)
KW  - ZGA (Other)
KW  - perinucleolar compartment (Other)
KW  - tRNA (Other)
KW  - tRNA-iMet (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39214079
DO  - DOI:10.1016/j.cell.2024.08.011
UR  - https://inrepo02.dkfz.de/record/292526
ER  -