| Autor: |
Febrimarsa, Gornik, Sebastian G, Barreira, Sofia N, Salinas‐Saavedra, Miguel, Schnitzler, Christine E, Baxevanis, Andreas D, Frank, Uri |
| Předmět: |
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| Zdroj: |
EMBO Journal; Aug2023, Vol. 42 Issue 15, p1-11, 11p |
| Abstrakt: |
N6‐methyldeoxyadenosine (6mA) is a chemical alteration of DNA, observed across all realms of life. Although the functions of 6mA are well understood in bacteria and protists, its roles in animal genomes have been controversial. We show that 6mA randomly accumulates in early embryos of the cnidarian Hydractinia symbiolongicarpus, with a peak at the 16‐cell stage followed by clearance to background levels two cell cycles later, at the 64‐cell stage—the embryonic stage at which zygotic genome activation occurs in this animal. Knocking down Alkbh1, a putative initiator of animal 6mA clearance, resulted in higher levels of 6mA at the 64‐cell stage and a delay in the initiation of zygotic transcription. Our data are consistent with 6mA originating from recycled nucleotides of degraded m6A‐marked maternal RNA postfertilization. Therefore, while 6mA does not function as an epigenetic mark in Hydractinia, its random incorporation into the early embryonic genome inhibits transcription. In turn, Alkbh1 functions as a genomic 6mA "cleaner," facilitating timely zygotic genome activation. Given the random nature of genomic 6mA accumulation and its ability to interfere with gene expression, defects in 6mA clearance may represent a hitherto unknown cause of various pathologies. Synopsis: The presence and functions of N6‐methylation of deoxyadenosine (6mA) in animal genomes are disputed. This study shows that N6‐methyladenosine (m6A)‐decorated maternal RNA is the source of 6mA in cnidarian embryonic genomes, from which it has to be removed for initiation of zygotic transcription.Rapid degradation of m6A‐marked maternal RNAs generates a nucleotide pool containing m6A.After NTP‐to‐dNTP conversion by a ribonucleotide reductase, 6mA is randomly incorporated into the embryonic genome.Genomic 6mA interferes with embryonic transcription.Removal of 6mA by the 6mA dioxygenase Alkbh1 facilitates timely zygotic genome activation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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