Randomly incorporated genomic N6-methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian.
Randomly incorporated genomic N6-methyldeoxyadenosine delays zygotic transcription initiation in a cnidarian.
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DOI：
10.15252/embj.2022112934
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发表时间：
2023-08-01
期刊：
影响因子：
11.4
通讯作者：
Frank, Uri
中科院分区：
文献类型：
--
作者：
Febrimarsa;Gornik, Sebastian G.;Barreira, Sofia N.;Salinas-Saavedra, Miguel;Schnitzler, Christine E.;Baxevanis, Andreas D.;Frank, Uri
N6-甲基脱氧腺苷（6 mA）是一种DNA的化学改变，在生命的各个领域都可以观察到。虽然6 mA在细菌和原生生物中的功能已经被很好地理解，但它在动物基因组中的作用一直存在争议。我们发现，6 mA随机积累在刺胞动物Hydractinia symbiolongalpus的早期胚胎中，在16细胞阶段达到峰值，然后在两个细胞周期后清除到背景水平，在64细胞阶段，在该动物中合子基因组激活发生的胚胎阶段。敲除Alkbh 1（动物6 mA清除的假定启动子）导致64细胞阶段的6 mA水平较高，合子转录启动延迟。我们的数据与6 mA来源于受精后降解的m6 A标记的母体RNA的再循环核苷酸一致。因此，虽然6 mA在Hydractinia中不起表观遗传标记的作用，但其随机掺入早期胚胎基因组抑制转录。反过来，Alkbh 1作为基因组6 mA“清洁剂”，促进合子基因组的及时激活。考虑到基因组6 mA积累的随机性质及其干扰基因表达的能力，6 mA清除的缺陷可能代表各种病理学的迄今未知原因。N6-甲基腺苷修饰的母体RNA是刺胞动物共生海葵胚胎基因组中6 mA的来源。
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. N6‐methyladenosine‐decorated maternal RNA is the source of 6mA in the embryonic genome of the cnidarian Hydractinia symbiolongicarpus.
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