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| Nucleosomes, which fold chromosomal DNA, contain two molecules each of the core histones H2A, H2B, H3, and H4. Almost two turns of DNA are wrapped around this octameric core, which represses transcription. The histone amino termini extend from the core, where they can be modified post-translationally by acetylation, phosphorylation, ubiquitination, and methylation, affecting their charge and function. Acetylation of the ε-amino groups of specific histone lysines is catalyzed by histone acetyltransferases (HATs) and correlates with an open chromatin structure and gene activation. Histone deacetylases (HDACs) catalyze the hydrolytic removal of acetyl groups from histone lysine residues and correlates with chromatin condensation and transcriptional repression. Therefore, HDAC inhibition results in transcriptional activation through the conformational relaxation of DNA. Changes in the transcription of key genes has linked HDAC inhibitors to blocking angiogenesis and cell cycling, and promoting apoptosis and differentiation. By targetingthese key components of tumor proliferation, HDAC inhibitors are currently being explored as potential anticancer agents. |