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Genome-wide profiling identifies a subset of methamphetamine (METH)-induced genes associated with METH-induced increased H4K5Ac binding in the rat striatum.
- Source :
-
BMC genomics [BMC Genomics] 2013 Aug 12; Vol. 14, pp. 545. Date of Electronic Publication: 2013 Aug 12. - Publication Year :
- 2013
-
Abstract
- Background: METH is an illicit drug of abuse that influences gene expression in the rat striatum. Histone modifications regulate gene transcription.<br />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.<br />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.<br />Conclusion: Acute METH injections caused increased gene expression of genes that showed increased H4K5Ac binding near their transcription start sites.
- Subjects :
- Acetylation
Animals
Chromatin Immunoprecipitation
Cytoskeletal Proteins metabolism
Gene Regulatory Networks
Genome-Wide Association Study
Male
Methamphetamine administration & dosage
Nerve Tissue Proteins metabolism
Protein Binding
Proto-Oncogene Proteins c-fos metabolism
Rats
Signal Transduction
Transcription, Genetic
Corpus Striatum drug effects
Corpus Striatum metabolism
Gene Expression Profiling
Gene Expression Regulation drug effects
Histones metabolism
Methamphetamine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2164
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- BMC genomics
- Publication Type :
- Academic Journal
- Accession number :
- 23937714
- Full Text :
- https://doi.org/10.1186/1471-2164-14-545