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Chromatin modification and disease
  1. Colin A Johnson
  1. Chromatin and Gene Expression Group, Department of Anatomy, University of Birmingham, Birmingham B15 2TT, UK
  1. Dr Johnson, c.a.johnson{at}

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Physicians consider that when they have discovered the cause of disease, they have also discovered the method of treating it.” Cicero, Tusculan Disputations, III.x.23.

In the last few years, the exciting realisation in the field of gene regulation is that transcription factors can function by recruiting large, multiprotein complexes which mediate several types of chromatin modification and remodelling events that alter the structure of chromatin. Chromatin structure changes include post-translational modifications of histones, DNA methylation, remodelling of the chromatin, and the maintenance of a heterochromatic or euchromatic state. Most of these events are brought about by enzymatic mechanisms. In general, the catalytic subunits are only one component of the complexes, with the distribution and localisation of the structural changes dependent on targeting components. Many of the catalytic components (sometimes called coactivators and corepressors) interact with the activator and repressor proteins that mediate the actual process of transcriptional regulation. Transcriptional dysregulation can therefore arise from mutations that cause the loss or perturbation of chromatin modification or remodelling, which are now known to have an important role in the pathogenesis of cancer and other genetic diseases. Some of the proteins that mediate these events are therefore novel molecular targets for future treatments.

In eukaryotes, DNA is packaged by histone proteins into nucleosomes, the fundamental repeating structural unit of chromatin.1The nucleosomal core particle consists of an octomeric complex of core histones (two each of H2A, H2B, H3, and H4) around which 147 bp of DNA is wrapped in 1.65 turns of a left handed superhelix.2 The minor and major grooves of adjacent turns of the DNA superhelix line up and form channels through which the histone N-termini domains protrude from the core. These regions are in the form of “tails” that appear to lack secondary structure3 and …

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