Nucleosome

A nucleosome is a basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight histone protein cores. This structure is often compared to thread wrapped around a spool. A nucleosome is a basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA wound in sequence around eight histone protein cores. This structure is often compared to thread wrapped around a spool. Nucleosomes form the fundamental repeating units of eukaryotic chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it (in mammalian cells approximately 2 m of linear DNA have to be packed into a nucleus of roughly 10 µm diameter). Nucleosomes are folded through a series of successively higher order structures to eventually form a chromosome; this both compacts DNA and creates an added layer of regulatory control, which ensures correct gene expression. Nucleosomes are thought to carry epigenetically inherited information in the form of covalent modifications of their core histones. Nucleosome positions in the genome are not random, and it is important to know where each nucleosome is located because this determines the accessibility of the DNA to regulatory proteins. Nucleosomes were first observed as particles in the electron microscope by Don and Ada Olins in 1974, and their existence and structure (as histone octamers surrounded by approximately 200 base pairs of DNA) were proposed by Roger Kornberg. The role of the nucleosome as a general gene repressor was demonstrated by Lorch et al. in vitro, and by Han and Grunstein in vivo in 1987 and 1988, respectively. The nucleosome core particle consists of approximately 146 base pairs (bp) of DNA wrapped in 1.67 left-handed superhelical turns around a histone octamer, consisting of 2 copies each of the core histones H2A, H2B, H3, and H4. Core particles are connected by stretches of linker DNA, which can be up to about 80 bp long. Technically, a nucleosome is defined as the core particle plus one of these linker regions; however the word is often synonymous with the core particle. Genome-wide nucleosome positioning maps are now available for many model organisms including mouse liver and brain. Linker histones such as H1 and its isoforms are involved in chromatin compaction and sit at the base of the nucleosome near the DNA entry and exit binding to the linker region of the DNA. Non-condensed nucleosomes without the linker histone resemble 'beads on a string of DNA' under an electron microscope. In contrast to most eukaryotic cells, mature sperm cells largely use protamines to package their genomic DNA, most likely to achieve an even higher packaging ratio. Histone equivalents and a simplified chromatin structure have also been found in Archea, suggesting that eukaryotes are not the only organisms that use nucleosomes. Pioneering structural studies in the 1980s by Aaron Klug's group provided the first evidence that an octamer of histone proteins wraps DNA around itself in about 1.7 turns of a left-handed superhelix. In 1997 the first near atomic resolution crystal structure of the nucleosome was solved by the Richmond group, showing the most important details of the particle. The human alpha-satellite palindromic DNA critical to achieving the 1997 nucleosome crystal structure was developed by the Bunick group at Oak Ridge National Laboratory in Tennessee. The structures of over 20 different nucleosome core particles have been solved to date, including those containing histone variants and histones from different species. The structure of the nucleosome core particle is remarkably conserved, and even a change of over 100 residues between frog and yeast histones results in electron density maps with an overall root mean square deviation of only 1.6Å. The nucleosome core particle (shown in the figure) consists of about 146 bp of DNA wrapped in 1.67 left-handed superhelical turns around the histone octamer, consisting of 2 copies each of the core histones H2A, H2B, H3, and H4. Adjacent nucleosomes are joined by a stretch of free DNA termed linker DNA (which varies from 10 - 80 bp in length depending on species and tissue type). Nucleosome core particles are observed when chromatin in interphase is treated to cause the chromatin to unfold partially. The resulting image, via an electron microscope, is 'beads on a string'. The string is the DNA, while each bead in the nucleosome is a core particle. The nucleosome core particle is composed of DNA and histone proteins.