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(PS2) BEYOND THE DOUBLE HELIX: WRITING AND READING THE HISTONE CODE. Allis, C. David1, 1 The Rockefeller University, New York, NY ABSTRACT- The human genome is estimated to contain 30,000 to 40,000 unique genes; the DNA sequence and chromosomal location of all these genes are becoming widely known. A central challenge facing the biomedical community is how to derive medically -valuable knowledge about the function of these genes from the now-available DNA sequence data. Though every gene exists within every cell in the human body, only a small percentage of genes are activated in any given cell. To manage this genetic information efficiently, nature has evolved a sophisticated system that facilitates access to specific genes. This system relies on a DNA-histone protein complex called chromatin to efficiently package the genetic information that exists within each cell. This packaging system making certain genes more readily accessible to transcription factors and other machinery that must engage our genetic template. Chromatin modifications, and the regulation of the enzymes responsible for adding or subtracting them, are poised to take center stage in the study of cancer in the current post-genomic or epigenomic era. Moreover, the implications of chromatin and its modification are beginning to be appreciated in clinical oncology. The identification of altered DNA methylation and histone acetylase activity in a range of human cancers, coupled with the use of HDAC inhibitors in the treatment of leukemia make a compelling argument. It is clear that the regulatory signals provided by chromatin modifications will revolutionize our view of cancer as new models of epigenetic carcinogenesis are advanced. We favor the view that there exists an epigenetic indexing system for our genome, or a histone code, that represents a fundamental regulatory mechanism that acts outside of the DNA itself. We predict that this code impacts on most, if not all, chromatin-templated processes with far-reaching consequences for cell fate decisions and for normal and pathological development (for reviews and references, see below). Most of our current research is centered around chromatin and its regulation though post-translational modification. KEY WORDS: chromatin, HDAC, histone, epigenetic |
