ABSTRACT
The DNA of eukaryotic cells is packaged into nucleosomes, the basic repeating unit of chromatin. The nucleosome can present an efficient barrier to all DNA-templated processes, including transcription, replication, and DNA repair, necessitating a dynamic chromatin structure that includes highly condensed heterochromatin and the more relaxed and accessible euchromatin. Nucleosomes are comprised of 147 base pairs of DNA wrapped 1.65 times around the globular core of the histone octamer which is assembled from two copies each of histones H2A, H2B, H3, and H4 [1]. Importantly, the N-terminal tail of each histone protrudes out from the cylindrically shaped nucleosomal core in an unstructured fashion and is accessible to nuclear proteins. These tails are the site of numerous, well-characterized covalent modifications of specific amino acid residues which, along with ATP-dependent chromosome remodeling complexes, function to regulate chromatin architecture and accessibility of the underlying DNA [2]. Mass spectrometry has revealed modification of histones in the globular region as well, and emerging evidence indicates a role for these modifications in the regulation of chromatin structure [3-7]. In addition, chromatin structure is affected by incorporation of histone variants that have specific effects on various DNA-based processes.
