Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes

• DOI: 10.1371/journal.pone.0139103
• Publication Date: 2015-09-28T13:43:22Z
• Authors: Amber N. Brown; Cynthia Vied; Jonathan H. Dennis; Pradeep G. Bhide
• Keywords: 0301 basic medicine; Nicotine; Base Sequence; Science; Q; R; Epigenesis, Genetic; Nucleosomes; 03 medical and health sciences; Gene Ontology; Cocaine; Gene Expression Regulation; Cell Line, Tumor; Medicine; Humans; Promoter Regions, Genetic; Research Article; Early Growth Response Protein 1

Drugs of abuse modify behavior by altering gene expression in the brain. Gene can be regulated changes DNA methylation as well histone modifications, which alter chromatin structure, compaction and accessibility. In order to better understand molecular mechanisms directing drug-induced we examined DNA-nucleosome interactions within promoter regions 858 genes human neuroblastoma cells (SH-SY5Y) exposed nicotine or cocaine. Widespread, drug- time-resolved repositioning nucleosomes was identified at transcription start site region multiple genes. Nicotine cocaine produced unique shared terms numbers types affected, sites could increase decrease probability based on Half nucleosome positions approximated a theoretical model occupancy physical chemical characteristics sequence, whereas basal drug naïve were generally sequence independent. Thus suggest that represents an initial dynamic genome-wide alteration transcriptional landscape preceding more selective downstream reprogramming, ultimately characterizes cell- tissue-specific responses drugs abuse.