دورية أكاديمية
أعرض في EDS

Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish.

التفاصيل البيبلوغرافية
العنوان: Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish.
المؤلفون: Kamstra JH; Faculty of Veterinary Medicine, Department of Basic Sciences and Aquatic Medicine, CoE CERAD, Norwegian University of Life Sciences, P.O. Box 8146 Dep., 0033 Oslo, Norway., Sales LB; Institute for Environmental Studies, VU University Amsterdam, Amsterdam, The Netherlands., Aleström P; Faculty of Veterinary Medicine, Department of Basic Sciences and Aquatic Medicine, CoE CERAD, Norwegian University of Life Sciences, P.O. Box 8146 Dep., 0033 Oslo, Norway., Legler J; Institute for Environmental Studies, VU University Amsterdam, Amsterdam, The Netherlands.; Institute for Environment, Health and Societies, College of Health and Life Sciences, Brunel University London, Uxbridge, UK.
المصدر: Epigenetics & chromatin [Epigenetics Chromatin] 2017 Apr 12; Vol. 10, pp. 20. Date of Electronic Publication: 2017 Apr 12 (Print Publication: 2017).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101471619 Publication Model: eCollection Cited Medium: Internet ISSN: 1756-8935 (Electronic) Linking ISSN: 17568935 NLM ISO Abbreviation: Epigenetics Chromatin Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central
مواضيع طبية MeSH: Azacitidine/*toxicity , DNA/*metabolism , DNA Methylation/*drug effects , Diethylhexyl Phthalate/*analogs & derivatives, Animals ; Brain/drug effects ; Brain/metabolism ; DNA/chemistry ; DNA/isolation & purification ; DNA (Cytosine-5-)-Methyltransferase 1/genetics ; DNA (Cytosine-5-)-Methyltransferase 1/metabolism ; Diethylhexyl Phthalate/toxicity ; Female ; Gene Expression Regulation, Developmental/drug effects ; Larva/drug effects ; Larva/growth & development ; Larva/metabolism ; Liver/drug effects ; Liver/metabolism ; Male ; Mutagenesis ; Pregnancy ; Sequence Analysis, DNA ; Spermatozoa/drug effects ; Spermatozoa/metabolism ; Zebrafish/genetics ; Zebrafish/growth & development ; Zebrafish Proteins/chemistry ; Zebrafish Proteins/metabolism
مستخلص: Background: Exposure to environmental stressors during development may lead to latent and transgenerational adverse health effects. To understand the role of DNA methylation in these effects, we used zebrafish as a vertebrate model to investigate heritable changes in DNA methylation following chemical-induced stress during early development. We exposed zebrafish embryos to non-embryotoxic concentrations of the biologically active phthalate metabolite mono(2-ethylhexyl) phthalate (MEHP, 30 µM) and the DNA methyltransferase 1 inhibitor 5-azacytidine (5AC, 10 µM). Direct, latent and transgenerational effects on DNA methylation were assessed using global, genome-wide and locus-specific DNA methylation analyses.
Results: Following direct exposure in zebrafish embryos from 0 to 6 days post-fertilization, genome-wide analysis revealed a multitude of differentially methylated regions, strongly enriched at conserved non-genic elements for both compounds. Pathways involved in adipogenesis were enriched with the putative obesogenic compound MEHP. Exposure to 5AC resulted in enrichment of pathways involved in embryonic development and transgenerational effects on larval body length. Locus-specific methylation analysis of 10 differentially methylated sites revealed six of these loci differentially methylated in sperm sampled from adult zebrafish exposed during development to 5AC, and in first and second generation larvae. With MEHP, consistent changes were found at 2 specific loci in first and second generation larvae.
Conclusions: Our results suggest a functional role for DNA methylation on cis-regulatory conserved elements following developmental exposure to compounds. Effects on these regions are potentially transferred to subsequent generations.
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فهرسة مساهمة: Keywords: 5-Azacytidine; DNA methylation; Environmental stress; Epigenetics; Phthalate; Toxicology; Transgenerational; Zebrafish
المشرفين على المادة: 0 (Zebrafish Proteins)
9007-49-2 (DNA)
C42K0PH13C (Diethylhexyl Phthalate)
EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
FU2EWB60RT (mono-(2-ethylhexyl)phthalate)
M801H13NRU (Azacitidine)
تواريخ الأحداث: Date Created: 20170418 Date Completed: 20180129 Latest Revision: 20231112
رمز التحديث: 20231112
مُعرف محوري في PubMed: PMC5389146
DOI: 10.1186/s13072-017-0126-4
PMID: 28413451
قاعدة البيانات: MEDLINE
الوصف
تدمد:1756-8935
DOI:10.1186/s13072-017-0126-4