TY - JOUR
T1 - The role of DNA methylation on gene expression in the vertebrae of ancestrally benzo[a]pyrene exposed F1 and F3 male medaka
AU - Wan, Teng
AU - Mo, Jiezhang
AU - Au, Doris Wai-Ting
AU - Qin, Xian
AU - Tam, Nathan Yi-Kan
AU - Kong, Richard Yuen-Chong
AU - Seemann, Frauke
PY - 2023
Y1 - 2023
N2 - 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. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
AB - 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. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
KW - Benzo[a]pyrene
KW - DNA methylation
KW - transgenerational effects
KW - REGULATES OSTEOBLAST DIFFERENTIATION
KW - POLYCYCLIC AROMATIC-HYDROCARBONS
KW - BONE-FORMATION
KW - TGF-BETA
KW - GROWTH-FACTOR
KW - TRANSGENERATIONAL INHERITANCE
KW - CELLS
KW - PROTEIN
KW - BENZO(A)PYRENE
KW - FISH
UR - http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=LinksAMR&SrcApp=PARTNER_APP&DestLinkType=FullRecord&DestApp=WOS&KeyUT=001006849100001
UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85163222854&origin=recordpage
UR - http://www.scopus.com/inward/record.url?scp=85163222854&partnerID=8YFLogxK
U2 - 10.1080/15592294.2023.2222246
DO - 10.1080/15592294.2023.2222246
M3 - RGC 21 - Publication in refereed journal
C2 - 37322851
SN - 1559-2294
VL - 18
JO - Epigenetics
JF - Epigenetics
IS - 1
M1 - ARTN 2222246
ER -