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Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian

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...

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Autores principales: Febrimarsa, Gornik, Sebastian G, Barreira, Sofia N, Salinas‐Saavedra, Miguel, Schnitzler, Christine E, Baxevanis, Andreas D, Frank, Uri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390872/
https://www.ncbi.nlm.nih.gov/pubmed/37708295
http://dx.doi.org/10.15252/embj.2022112934
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author Febrimarsa
Gornik, Sebastian G
Barreira, Sofia N
Salinas‐Saavedra, Miguel
Schnitzler, Christine E
Baxevanis, Andreas D
Frank, Uri
author_facet Febrimarsa
Gornik, Sebastian G
Barreira, Sofia N
Salinas‐Saavedra, Miguel
Schnitzler, Christine E
Baxevanis, Andreas D
Frank, Uri
author_sort Febrimarsa
collection PubMed
description 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.
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spelling pubmed-103908722023-08-02 Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian Febrimarsa Gornik, Sebastian G Barreira, Sofia N Salinas‐Saavedra, Miguel Schnitzler, Christine E Baxevanis, Andreas D Frank, Uri EMBO J Articles 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. John Wiley and Sons Inc. 2023-07-04 /pmc/articles/PMC10390872/ /pubmed/37708295 http://dx.doi.org/10.15252/embj.2022112934 Text en © 2023 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Febrimarsa
Gornik, Sebastian G
Barreira, Sofia N
Salinas‐Saavedra, Miguel
Schnitzler, Christine E
Baxevanis, Andreas D
Frank, Uri
Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title_full Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title_fullStr Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title_full_unstemmed Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title_short Randomly incorporated genomic N6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
title_sort randomly incorporated genomic n6‐methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390872/
https://www.ncbi.nlm.nih.gov/pubmed/37708295
http://dx.doi.org/10.15252/embj.2022112934
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