| Description : |
DNA is organized into a nucleoprotein complex termed chromatin, which not only is involved with the compaction of DNA within the nucleus but also serves as an important means to regulate genome function. The basic unit of chromatin is the nucleosome. Each nucleosome core contains 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 lysine residues, is catalyzed by histone acetyltransferases (HATs) producing a histone modification that 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. Functional defects of either of these enzymes can lead to several diseases, ranging from cancer to neurodenerative dieases. HATs and HDACs thus are potential therapeutic targets. |
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