| Scientific Background: | The nucleosome is made up of four core histone proteins (H2A, H2B, H3 and H4) and is the primary building block of chromatin. The core histones form an octamer which is made up of one H3-H4 tetramer and two H2A-H2B dimers. The C-terminal domains of the core histones have very similar conformations that are important for nucleosome assembly. The N-terminal tails are less structured which is thought to allow for dynamic changes in the accessibility of the underlying genome. The N-terminal tail of core histones undergo different posttranscriptional modifications including acetylation, phosphorylation, methylation and ubiquitination. These modifications occur in response to cell signal stimuli and have a direct effect on gene expression. Histone H2B is primarily acetylated at lysines 5, 12, 15 and 20. histone H2B is phosphorylated in apoptotic cells and this event occurs around the time of nucleosomal DNA fragmentation. Phosphorylation of both histone H2A.X and H2B is dependant on caspase activation and therefore may be linked to caspase-induced signalling pathways. |
