X-ray crystallographic analysis of the chromatosome

The packaging of eukaryotic DNA into chromatin consists of the nucleosome as the basic repeating unit.The nucleosome has a core region, comprised of ~146 base pairs of DNA wrapped around a protein octamer of core histones, in addition to a variable length of linker DNA.The linker DNA connecting adjacent nucleosome core regions is on average ~50 base pairs in length in higher eukaryotes and can be occupied by a linker histone.By modulating chromatin structure, dynamics and recognition by other nuclear factors, the core and linker histones regulate genomic function.The first atomic model of the nucleosome core (particle) was published in 1997 [1], paving the way for the structural solution of a great variety of nucleosome core constructs composed of variant/modified histones and different DNA sequences [2,3].This has consequently revolutionized our understanding of nucleosome activity, and yet 19 years later we are still lacking an atomic level understanding of how linker histones interact with nucleosomes.In mammals, there are 11 linker histone variants, which can display cell type and cellular status dependent expression, site-specific localization in the nucleus as well as specific interactions with different nuclear factors to foster gene-specific regulation.In addition, the linker histones can undergo an enormity of post-translational modifications that further expand the regulatory landscape.Nonetheless, the general function of the linker histones is largely that of compacting nucleosomes into condensed chromatin states, which are generally repressive to gene expression.An atomic model of the chromatosome, the minimal assembly of a nucleosome with a linker histone, could significantly advance our understanding of chromatin function, and we present here the first X-ray crystal structure of a chromatosome [4].[1]