Front Neurosci. 2020 Nov 25;14:591196. doi: 10.3389/fnins.2020.591196. eCollection 2020.
Anticonvulsants and Chromatin-Genes Expression: A Systems Biology Investigation.
Frontiers in neuroscience
Thayne Woycinck Kowalski, Julia do Amaral Gomes, Mariléa Furtado Feira, Ágata de Vargas Dupont, Mariana Recamonde-Mendoza, Fernanda Sales Luiz Vianna
Affiliations
Affiliations
- Postgraduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- Laboratory of Immunobiology and Immunogenetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
- National Institute of Population Medical Genetics (INAGEMP), Porto Alegre, Brazil.
- Genomic Medicine Laboratory, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
- National System of Information on Teratogenic Agents (SIAT), Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
- Centro Universitário CESUCA, Cachoeirinha, Brazil.
- Bioinformatics Core, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.
- Institute of Informatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
PMID: 33328862
PMCID: PMC7732676 DOI: 10.3389/fnins.2020.591196
Abstract
Embryofetal development is a critical process that needs a strict epigenetic control, however, perturbations in this balance might lead to the occurrence of congenital anomalies. It is known that anticonvulsants potentially affect epigenetics-related genes, however, it is not comprehended whether this unbalance could explain the anticonvulsants-induced fetal syndromes. In the present study, we aimed to evaluate the expression of epigenetics-related genes in valproic acid, carbamazepine, or phenytoin exposure. We selected these three anticonvulsants exposure assays, which used murine or human embryonic stem-cells and were publicly available in genomic databases. We performed a differential gene expression (DGE) and weighted gene co-expression network analysis (WGCNA), focusing on epigenetics-related genes. Few epigenetics genes were differentially expressed in the anticonvulsants' exposure, however, the WGCNA strategy demonstrated a high enrichment of chromatin remodeling genes for the three drugs. We also identified an association of 46 genes related to Fetal Valproate Syndrome, containing
Copyright © 2020 Kowalski, Gomes, Feira, Dupont, Recamonde-Mendoza and Vianna.
Keywords: WGCNA; antiepileptics; epigenetics; fetal hydantoin syndrome; fetal valproate syndrome; phenytoin; teratogen; valproic acid
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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