Nucleosome

The packaging structure of the DNA in eukaryotic cells is a complex of DNA and histones snRNA, called the nucleosome. From Ada and Donald Olins discovered swollen nuclei in electron microscopic images and first presented in 1973 on the " Third Annual Meeting of the American Society for Cell Biology" as " ν - body" ( new particles), this was almost immediately in as fundamental packing unit of DNA chromatin accepted.

Discovery and properties

1974 get several teams, including that of Roger Kornberg, analyzes that showed the structure of these particles from a histone octamer, a linker histone and about 160-200 base pairs of DNA. 1975 this unit was introduced as a nucleosome. 1974 is now regarded as the birth year of molecular epigenetics.

In addition to interactions that lead to compaction of DNA, histones interactions go one under the other. Then the Nukleosomenkern (the " core particle" ) made of two copies of the histones H2A, H2B, H3 and H4 are formed at the at 1.75 turns 146 base pairs of DNA are wrapped. The space between two nucleosomes ( the variable "linker", which may comprise between 160 base pairs in yeast and 200 base pairs in higher organisms in humans are 50-60 base pairs) is occupied by another histone H1, which is higher in the construction structures ( the so-called 30 - nm fiber, explains, for example, in the " solenoid " model) is involved. The components of the Nukleosomenkerns were ( distinguish only two amino acid residues of the histone H3 of the people from that of the pea) in the evolution of highly conserved, the fundamental importance of this unit (and its modifications - see below ) highlights.

The figure shows the schematic structure of the nucleosome and its structural variability again. The histone core forms a cylinder of diameter 11 nm and 5 nm height ( blue). The predominantly lysine - and arginine - rich and thus positively charged N -terminal tails of histones (the " histone - tails" ) bind to the negatively charged backbone of the DNA phosphate groups, thus the accessibility of transcription factors is limited. Acetylation of lysine residues by acetyltransferases eliminates their positive charge and gives the previously concealed information freely; simultaneously learns the Nukleosomenkern a structural change (red). This simplistic charge model is now at least controversial. Recent research shows that the modified designs can be read by various proteins, and this leads to the activation or repression of genes affected. The acetylation state itself is determined by the balance of histone acetyltransferases ( HATs ) and histone deacetylases ( HDACs ) - the latter by a specific inhibitors such as are: Trichostatin A ( TSA) or butyrate inhibited, so dominate the former. Such experimental approaches have led to the experimental demonstration of this fact.

Work on the structure of the nucleosomes were taken by Aaron Klug (Nobel Prize 1982 for the crystal structure analyzes of protein / nucleic acid complexes ) in London at the Medical Research Council. This work led in 1984 at relatively low resolution for the first proposed structure. The works have since been systematically driven by Timothy Richmond, who has been involved in the group of Klug, 1984 to the first proposed structure, at the Institute for Molecular Biology & Biophysics at the ETH Zurich. In 1997, the Working Group of Richmond published a structure of the nucleosome at a resolution of 2.8 Å and 2002 was followed by the publication of the structure with a resolution of 1.9 Å.

In 2005, the Working Group of Richmond published an X-ray crystal structure of the Tetranukleosoms.