Epigenetic mechanisms in central nervous system disorders



  • Epigenetic regulation of chromatin structure results in the stable maintenance of gene expression via covalent modifications of the DNA or its associated histone proteins (reviewed in Jiang et al. 2008). Within the nucleus the DNA interacts with histone proteins within the nucleosome core. Histones, being positively charged, associate with the negatively charged phosphodiester backbone of DNA to result in a highly compacted nucleosome structure known as chromatin. The unraveling of compacted chromatin is necessary for gene transcription to occur and is subject to environmental influences (Colvis et al. 2005; Jiang et al. 2008; Levenson and Sweatt 2005; Tsankova et al. 2007; Weaver et al. 2006). Chromatin structure regulation or chromatin remodeling is the molecular correlate of the transitioning between densely packed heterochromatin (closed to gene transcription) and loosely packed euchromatin (open to gene transcription). Conversion of heterochromatin to its more open form, euchromatin, involves the unraveling of the chromatin structure and making the DNA accessible to co-activator complexes and the transcriptional machinery. Here we explore the epigenetic manipulating compounds affecting chromatin remodeling and their ability to influence gene transcription. Such compounds offer a novel therapeutic approach for the treatment of altered chromatin structure regulation in CNS disorders.
  • Authors

    Digital Object Identifier (doi)

    International Standard Book Number (isbn) 13

  • 9780521519762
  • Start Page

  • 321
  • End Page

  • 333
  • Volume

  • 9780521519762