Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1785082573126369280 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10390872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT febrimarsa randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT gorniksebastiang randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT barreirasofian randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT salinassaavedramiguel randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT schnitzlerchristinee randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT baxevanisandreasd randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian AT frankuri randomlyincorporatedgenomicn6methyldeoxyadenosinedelayszygotictranscriptioninitiationinacnidarian |