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To regulate the precise pattern of gene expression during development, eukaryotic cells have evolved to have multifaceted transcriptional machineries and chromatin states. The DNA within the eukaryotic nucleus is found in complex with histone proteins to form nucleosomes, the basic unit of chromatin. Detailed structural studies demonstrated that the N-terminal tails of each of the histones protrude outward beyond the gyres of DNA and can be posttranslationally modified. The modifications of histone tails could provide a landing pad for a diverse array of transcription factors, chromatin remodelers, and DNA-interacting proteins to regulate gene expression. Translocations and/or mutations in chromatin-modifying machineries that perturb the timing and/or pattern of gene expression can result in the pathogenesis of human diseases including cancer. Recent studies demonstrate that the misregulation of several of the histone-modifying enzymes can contribute to changes in the epigenetic state leading to disease development. Therefore, both the scientific and the pharmaceutical communities have concentrated on identifying the molecular function for many of the histone-modifying machineries and are in the process of developing small molecular inhibitors of their activities in the hope of their use for targeted therapeutics of cancer. This Keystone Symposia meeting on Epigenetic Marks and Cancer Drugs serves as a much-needed platform for bringing both the scientific and the pharmaceutical communities together to discuss recent advances in this very exciting area.
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