Scientists have analyzed in mice genomic profiles of various epigenetic marks of chromatin, the set of DNA and proteins found in the nucleus of eukaryotic cells in response to a family of drugs, inhibitors of histone deacetylase enzymes ( HDACi), which could represent an effective tool for the treatment of diseases affecting the nervous system.
The study describes the impact of the genomic level profiles HDACi in histone acetylation, a process related to the regulation of gene transcription or expression. "Taken together, our results illuminate both the relationship between gene expression and histone acetylation, as the mechanisms of action of these drugs neuropsychiatric" CSIC researchers say Angel Boat and Jose Lopez, who work at the Institute of Neuroscience ( joint CSIC and the University Miguel Hernández).
In a second study published in The Journal of Neuroscience, researchers have determined first genome-wide epigenetic alterations associated with Huntington's disease and its relationship failures genome expression also observed in this disease hereditary degenerative disease of the brain.
"The result of these experiments has revealed that defects in transcription and histone acetylation are two independent manifestations of the disease affecting a large number of genes, but that converge in a small number ofgenes," says CSIC researcher Luis Miguel value.
"These genes altered in both processes are particularly important to the development of the disease and therefore represent new targets for the development of drugs or therapies" adds Angel Barco. The study also provides new clues to understanding the mechanism of action of HDACi drugs in the treatment of Huntington's disease allowing therefore improve its specificity.
- Jose P. Lopez-Atalaya, Satomi Ito, Luis M. Valor, Eva Benito, y Ángel Barco. Genomic targets, and histone acetylation and gene expression profiling of neural HDAC inhibition. Nucl. Acids Res. DOI:10.1093/nar/gkt590.
- Valor LM, Guiretti D, López-Atalaya JP, Barco A. Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease. Journal of Neuroscience. DOI: 33(25):10471-10482.