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Open Access Research article

Genome-wide profiling identifies a subset of methamphetamine (METH)-induced genes associated with METH-induced increased H4K5Ac binding in the rat striatum

Jean Lud Cadet1*, Subramaniam Jayanthi1, Michael T McCoy1, Bruce Ladenheim1, Fabienne Saint-Preux1, Elin Lehrmann2, Supriyo De2, Kevin G Becker2 and Christie Brannock1

Author Affiliations

1 Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, 251 Bayview Boulevard, Baltimore, MD 21224, USA

2 Gene Expression and Genomics Unit, Intramural Research Program, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 21224, USA

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BMC Genomics 2013, 14:545  doi:10.1186/1471-2164-14-545

Published: 12 August 2013

Abstract

Background

METH is an illicit drug of abuse that influences gene expression in the rat striatum. Histone modifications regulate gene transcription.

Methods

We therefore used microarray analysis and genome-scale approaches to examine potential relationships between the effects of METH on gene expression and on DNA binding of histone H4 acetylated at lysine 4 (H4K5Ac) in the rat dorsal striatum of METH-naïve and METH-pretreated rats.

Results

Acute and chronic METH administration caused differential changes in striatal gene expression. METH also increased H4K5Ac binding around the transcriptional start sites (TSSs) of genes in the rat striatum. In order to relate gene expression to histone acetylation, we binned genes of similar expression into groups of 100 genes and proceeded to relate gene expression to H4K5Ac binding. We found a positive correlation between gene expression and H4K5Ac binding in the striatum of control rats. Similar correlations were observed in METH-treated rats. Genes that showed acute METH-induced increased expression in saline-pretreated rats also showed METH-induced increased H4K5Ac binding. The acute METH injection caused similar increases in H4K5Ac binding in METH-pretreated rats, without affecting gene expression to the same degree. Finally, genes that showed METH-induced decreased expression exhibited either decreases or no changes in H4K5Ac binding.

Conclusion

Acute METH injections caused increased gene expression of genes that showed increased H4K5Ac binding near their transcription start sites.

Keywords:
ChIP sequencing; Neural networks; Epigenetics; Histone acetylation; Microarray