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Nucleosome Repositioning

Title: Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.
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Name(s): Brown, Amber N, author
Vied, Cynthia, author
Dennis, Jonathan H, author
Bhide, Pradeep G, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2015-09-28
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y) exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.
Identifier: FSU_pmch_26414157 (IID), 10.1371/journal.pone.0139103 (DOI), PMC4586372 (PMCID), 26414157 (RID), 26414157 (EID), PONE-D-14-52968 (PII)
Grant Number: R01 DA033775
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4586372.
Subject(s): Base Sequence
Cell Line, Tumor
Cocaine/pharmacology
Early Growth Response Protein 1/genetics
Epigenesis, Genetic/drug effects
Gene Expression Regulation/drug effects
Gene Ontology
Humans
Nicotine/pharmacology
Nucleosomes/drug effects
Nucleosomes/metabolism
Promoter Regions, Genetic/genetics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26414157
Owner Institution: FSU
Is Part Of: PloS one.
1932-6203
Issue: iss. 9, vol. 10

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Brown, A. N., Vied, C., Dennis, J. H., & Bhide, P. G. (2015). Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes. Plos One. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26414157