Epigenetic effects of drugs on early human neural development
Epigenetic effects of drugs on early human neural development
No Thumbnail Available
Files
There are no files associated with this item.
Date
2015
Authors
Editors
Journal ISSN
Electronic ISSN
ISBN
Bibliographical data
Publisher
Series
DOI (citable link)
International patent number
Link to the license
EU project number
Project
Open Access publication
Collections
Title in another language
Publication type
Journal article
Publication status
Published
Published in
Neurotoxicology and Teratology ; 49 (2015). - pp. 144. - Elsevier. - ISSN 1872-9738. - eISSN 0892-0362
Abstract
The phenotype and function of cells are dependent on the sets of genes that are active or silenced in a given cell type. One important determinant of gene activity is signaling processes that lead to the activation of transcription factors. However, gene activity is also determined by the local chromatin structure. Epigenetic modifications, such as the methylation of DNA bases, or the posttranslational modification of histone proteins strongly affect the chromatin. Such chromatin changes have been little considered yet as target of neurotoxicants. We examined here, how the developmental neurotoxicant valproic acid, and other histone deacetylase inhibitors affected epigenetic modifications at the promoters of key developmental genes (e.g. Pax6). As model system, we used human pluripotent stem cells developing to neural precursor cells, i.e. a developmental stage corresponding to the early neural tube in fetuses. We identified epigenetic changes related to transient drug effects (histone acetylation), and other histone modifications (lysine methylation) that correlated well with permanent developmental disturbances. The findings of persistent methylation changes after drug exposure offer an explanation for persistent drug effects on neurodevelopment even after the initial drug exposure has ended.
Summary in another language
Subject (DDC)
570 Biosciences, Biology
Keywords
Conference
Review
undefined / . - undefined, undefined. - (undefined; undefined)
Cite This
ISO 690
LEIST, Marcel, 2015. Epigenetic effects of drugs on early human neural development. In: Neurotoxicology and Teratology. Elsevier. 49, pp. 144. ISSN 1872-9738. eISSN 0892-0362. Available under: doi: 10.1016/j.ntt.2015.04.140BibTex
@article{Leist2015Epige-52662, year={2015}, doi={10.1016/j.ntt.2015.04.140}, title={Epigenetic effects of drugs on early human neural development}, volume={49}, issn={1872-9738}, journal={Neurotoxicology and Teratology}, author={Leist, Marcel}, note={Meeting Abstract} }
RDF
<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/server/rdf/resource/123456789/52662"> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/52662"/> <dc:contributor>Leist, Marcel</dc:contributor> <dc:creator>Leist, Marcel</dc:creator> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-02-01T12:29:32Z</dcterms:available> <dc:rights>terms-of-use</dc:rights> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dcterms:title>Epigenetic effects of drugs on early human neural development</dcterms:title> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/server/rdf/resource/123456789/28"/> <dcterms:abstract xml:lang="eng">The phenotype and function of cells are dependent on the sets of genes that are active or silenced in a given cell type. One important determinant of gene activity is signaling processes that lead to the activation of transcription factors. However, gene activity is also determined by the local chromatin structure. Epigenetic modifications, such as the methylation of DNA bases, or the posttranslational modification of histone proteins strongly affect the chromatin. Such chromatin changes have been little considered yet as target of neurotoxicants. We examined here, how the developmental neurotoxicant valproic acid, and other histone deacetylase inhibitors affected epigenetic modifications at the promoters of key developmental genes (e.g. Pax6). As model system, we used human pluripotent stem cells developing to neural precursor cells, i.e. a developmental stage corresponding to the early neural tube in fetuses. We identified epigenetic changes related to transient drug effects (histone acetylation), and other histone modifications (lysine methylation) that correlated well with permanent developmental disturbances. The findings of persistent methylation changes after drug exposure offer an explanation for persistent drug effects on neurodevelopment even after the initial drug exposure has ended.</dcterms:abstract> <dcterms:issued>2015</dcterms:issued> <foaf:homepage rdf:resource="http://localhost:8080/"/> <dc:language>eng</dc:language> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2021-02-01T12:29:32Z</dc:date> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> </rdf:Description> </rdf:RDF>
Internal note
xmlui.Submission.submit.DescribeStep.inputForms.label.kops_note_fromSubmitter
Examination date of dissertation
Method of financing
Comment on publication
Meeting Abstract
Alliance license
Corresponding Authors der Uni Konstanz vorhanden
International Co-Authors
Bibliography of Konstanz
Yes
Refereed
No