Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure

BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Yun Huang [verfasserIn] Shanshan Lin [verfasserIn] Chengrong Wang [verfasserIn] Xin Pi [verfasserIn] Lei Jin [verfasserIn] Zhiwen Li [verfasserIn] Linlin Wang [verfasserIn] Aiguo Ren [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress

Übergeordnetes Werk:	In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 8(2020)
Übergeordnetes Werk:	volume:8 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcell.2020.582661

Katalog-ID:	DOAJ040867633

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520			\|a BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation.
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allfields	10.3389/fcell.2020.582661 doi (DE-627)DOAJ040867633 (DE-599)DOAJc9aec1b66edc41afbd6cbb4895124468 DE-627 ger DE-627 rakwb eng QH301-705.5 Yun Huang verfasserin aut Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General) Yun Huang verfasserin aut Shanshan Lin verfasserin aut Shanshan Lin verfasserin aut Chengrong Wang verfasserin aut Xin Pi verfasserin aut Lei Jin verfasserin aut Zhiwen Li verfasserin aut Linlin Wang verfasserin aut Aiguo Ren verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 8(2020) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:8 year:2020 https://doi.org/10.3389/fcell.2020.582661 kostenfrei https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2020
spelling	10.3389/fcell.2020.582661 doi (DE-627)DOAJ040867633 (DE-599)DOAJc9aec1b66edc41afbd6cbb4895124468 DE-627 ger DE-627 rakwb eng QH301-705.5 Yun Huang verfasserin aut Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General) Yun Huang verfasserin aut Shanshan Lin verfasserin aut Shanshan Lin verfasserin aut Chengrong Wang verfasserin aut Xin Pi verfasserin aut Lei Jin verfasserin aut Zhiwen Li verfasserin aut Linlin Wang verfasserin aut Aiguo Ren verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 8(2020) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:8 year:2020 https://doi.org/10.3389/fcell.2020.582661 kostenfrei https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2020
allfields_unstemmed	10.3389/fcell.2020.582661 doi (DE-627)DOAJ040867633 (DE-599)DOAJc9aec1b66edc41afbd6cbb4895124468 DE-627 ger DE-627 rakwb eng QH301-705.5 Yun Huang verfasserin aut Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General) Yun Huang verfasserin aut Shanshan Lin verfasserin aut Shanshan Lin verfasserin aut Chengrong Wang verfasserin aut Xin Pi verfasserin aut Lei Jin verfasserin aut Zhiwen Li verfasserin aut Linlin Wang verfasserin aut Aiguo Ren verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 8(2020) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:8 year:2020 https://doi.org/10.3389/fcell.2020.582661 kostenfrei https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2020
allfieldsGer	10.3389/fcell.2020.582661 doi (DE-627)DOAJ040867633 (DE-599)DOAJc9aec1b66edc41afbd6cbb4895124468 DE-627 ger DE-627 rakwb eng QH301-705.5 Yun Huang verfasserin aut Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General) Yun Huang verfasserin aut Shanshan Lin verfasserin aut Shanshan Lin verfasserin aut Chengrong Wang verfasserin aut Xin Pi verfasserin aut Lei Jin verfasserin aut Zhiwen Li verfasserin aut Linlin Wang verfasserin aut Aiguo Ren verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 8(2020) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:8 year:2020 https://doi.org/10.3389/fcell.2020.582661 kostenfrei https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2020
allfieldsSound	10.3389/fcell.2020.582661 doi (DE-627)DOAJ040867633 (DE-599)DOAJc9aec1b66edc41afbd6cbb4895124468 DE-627 ger DE-627 rakwb eng QH301-705.5 Yun Huang verfasserin aut Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation. neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General) Yun Huang verfasserin aut Shanshan Lin verfasserin aut Shanshan Lin verfasserin aut Chengrong Wang verfasserin aut Xin Pi verfasserin aut Lei Jin verfasserin aut Zhiwen Li verfasserin aut Linlin Wang verfasserin aut Aiguo Ren verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 8(2020) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:8 year:2020 https://doi.org/10.3389/fcell.2020.582661 kostenfrei https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 kostenfrei https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2020
language	English
source	In Frontiers in Cell and Developmental Biology 8(2020) volume:8 year:2020
sourceStr	In Frontiers in Cell and Developmental Biology 8(2020) volume:8 year:2020
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress Biology (General)
isfreeaccess_bool	true
container_title	Frontiers in Cell and Developmental Biology
authorswithroles_txt_mv	Yun Huang @@aut@@ Shanshan Lin @@aut@@ Chengrong Wang @@aut@@ Xin Pi @@aut@@ Lei Jin @@aut@@ Zhiwen Li @@aut@@ Linlin Wang @@aut@@ Aiguo Ren @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	770398138
id	DOAJ040867633
language_de	englisch
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Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p &lt; 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p &lt; 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. 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callnumber-first	Q - Science
author	Yun Huang
spellingShingle	Yun Huang misc QH301-705.5 misc neural tube defects misc DNA methylation misc polycyclic aromatic hydrocarbons misc Zic4 misc oxidative stress misc Biology (General) Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure
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topic_title	QH301-705.5 Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure neural tube defects DNA methylation polycyclic aromatic hydrocarbons Zic4 oxidative stress
topic	misc QH301-705.5 misc neural tube defects misc DNA methylation misc polycyclic aromatic hydrocarbons misc Zic4 misc oxidative stress misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc neural tube defects misc DNA methylation misc polycyclic aromatic hydrocarbons misc Zic4 misc oxidative stress misc Biology (General)
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title	Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure
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title_full	Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure
author_sort	Yun Huang
journal	Frontiers in Cell and Developmental Biology
journalStr	Frontiers in Cell and Developmental Biology
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author_browse	Yun Huang Shanshan Lin Chengrong Wang Xin Pi Lei Jin Zhiwen Li Linlin Wang Aiguo Ren
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author-letter	Yun Huang
doi_str_mv	10.3389/fcell.2020.582661
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title_sort	neural tube defects and zic4 hypomethylation in relation to polycyclic aromatic hydrocarbon exposure
callnumber	QH301-705.5
title_auth	Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure
abstract	BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation.
abstractGer	BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation.
abstract_unstemmed	BackgroundEpigenetic dysregulation is one of the postulated underlying mechanisms of neural tube defects (NTDs). Polycyclic aromatic hydrocarbons (PAHs), a group of environmental pollutants that are reported as a risk factor of NTDs, may cause decreased genome-wide DNA methylation. With DNA extracted from neural tissues, this study identified gene(s) whose hypomethylation was related to elevated risk for NTDs and examined whether its hypomethylation is related to PAH exposure.ResultsUsing data profiled by Infinium HumanMethylation450 BeadChip array from 10 NTD cases and eight controls, ZIC4, CASP8, RAB32, RARA, and TRAF6 were identified to be the top five genes in NTD-related hypomethylated gene families. Among all identified genes, ZIC4 had the largest number of differently methylated CpG sites (n = 13) in the promoter region and 5′ UTR. Significantly decreased methylation in the ZIC4 promoter region and 5′ UTR was verified in an independent cohort of 80 cases and 32 controls (p < 0.001) utilizing the Sequenom EpiTYPER platform. Hypomethylation of ZIC4 was associated with a higher risk of NTDs [adjusted OR = 1.08; 95% confidence interval (CI): 1.03, 1.13] in a logistic regression model. Mean methylation levels in the promoter region and 5′ UTR of ZIC4 tended to be inversely associated with levels of high-molecular-weight PAHs in fetal liver among NTD fetuses (β [95% CI]: −0.045 [−0.091, 0.001], p = 0.054). Six and three CpG sites in the ZIC4 promoter region and 5′ UTR were inversely correlated with antioxidant indicators and protein oxidation markers (ρ: −0.45 to −0.75, p < 0.05) in fetal neural tissues, respectively. In a whole-embryo cultured mouse model, hypomethylation of the Zic4 promoter region and 5′ UTR and upregulation of Zic4 were observed, coupled with increased NTD rates after BaP exposure. The antioxidant N-acetyl-L-cysteine normalized the changes observed in the BaP exposure group.ConclusionHypomethylation of the ZIC4 promoter region and 5′ UTR may increase the risk for NTDs; oxidative stress is likely to play a role in the methylation change of Zic4 in response to PAH exposure in NTD formation.
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title_short	Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure
url	https://doi.org/10.3389/fcell.2020.582661 https://doaj.org/article/c9aec1b66edc41afbd6cbb4895124468 https://www.frontiersin.org/articles/10.3389/fcell.2020.582661/full https://doaj.org/toc/2296-634X
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up_date	2024-07-03T17:11:10.200Z
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Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure

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