The role of DNA methylation on gene expression in the vertebrae of ancestrally benzo[a]pyrene exposed F1 and F3 male medaka.

The role of DNA methylation on gene expression in the vertebrae of ancestrally benzo[a]pyrene exposed F1 and F3 male medaka.
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DOI:
10.1080/15592294.2023.2222246
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发表时间:
2023-12
期刊:
影响因子:
3.7
通讯作者:
Seemann, Frauke
Seemann, Frauke
中科院分区:
生物学3区
文献类型:
--
作者:
Wan, Teng;Mo, Jiezhang;Au, Doris Wai-Ting;Qin, Xian;Tam, Nathan Yi-Kan;Kong, Richard Yuen-Chong;Seemann, Frauke

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苯并[a]芘(BaP)广泛存在于水环境中,并已被鉴定为骨毒物。先前的研究表明,祖先的苯并(a)芘暴露可导致鱼类跨代骨骼畸形。跨代效应被认为是由可遗传的表观遗传变化引起的,如DNA甲基化、组蛋白修饰和非编码RNA。为了研究DNA甲基化在苯并(a)芘诱导的跨代骨骼畸形中的作用以及畸形椎骨中相关的转录组学变化,我们使用高通量RNA测序(RNA-seq)和全基因组亚硫酸氢盐测序(WGBS)检查了雄性F1和F3青鳉鱼的椎骨。组织学结果显示,与对照组相比,在BaP衍生的F1和F3成年雄性中,椎骨处的成骨细胞数量减少。鉴定了与成骨细胞生成(F1和F3)、软骨生成(F1和F3)和破骨细胞生成(F3)相关的差异甲基化基因(DMG)。然而,RNA-seq数据并不支持DNA甲基化在调控骨骼发生相关基因中的作用,因为差异甲基化水平与骨骼发生相关基因表达谱之间的相关性很小。虽然DNA甲基化在基因表达的表观遗传调控中起着重要作用,但目前研究中观察到的椎骨基因表达模式的失调最有可能是由组蛋白修饰和miRNA介导的。值得注意的是,RNA-seq和WGBS数据表明,与神经系统发育相关的基因对祖先BaP暴露更敏感,表明对祖先BaP暴露的反应更复杂的跨代表型。
Benzo[a]pyrene (BaP) is ubiquitously present in the aquatic environment and has been identified as a bone toxicant. Previous studies have demonstrated that ancestral BaP exposure can cause transgenerational bone deformities in fish. Transgenerational effects are thought to be caused by heritable epigenetic changes, such as DNA methylation, histone modification, and non-coding RNAs. To investigate the role of DNA methylation in BaP-induced transgenerational skeletal deformities and the related transcriptomic changes in deformed vertebrae, we examined the vertebrae of male F1 and F3 medaka fish using high-throughput RNA sequencing (RNA-seq) and whole-genome bisulphite sequencing (WGBS). The histological results revealed that osteoblast numbers at the vertebral bone decreased in the BaP-derived F1 and F3 adult males in comparison with the control group. Differentially methylated genes (DMGs) associated with osteoblastogenesis (F1 and F3), chondrogenesis (F1 and F3), and osteoclastogenesis (F3) were identified. However, RNA-seq data did not support the role of DNA methylation in the regulation of genes involved in skeletogenesis since there was very little correlation between the level of differential methylation and gene expression profiles related to skeletogenesis. Although DNA methylation plays a major role in the epigenetic regulation of gene expression, the dysregulation of vertebral gene expression patterns observed in the current study is most likely to be mediated by histone modification and miRNAs. Notably, RNA-seq and WGBS data indicated that genes related to nervous system development are more sensitive to ancestral BaP exposure, indicating a more complex transgenerational phenotype in response to ancestral BaP exposure.
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期刊: ADVANCES IN MOLECULAR TOXICOLOGY, VOL 6
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