Packaging of DNA Helix

The DNA inside even a single mammalian cell is astonishingly long relative to the space available to hold it: the distance between two consecutive base pairs along the double helix is a fixed 0.34 nanometres, so multiplying this spacing by the total number of base pairs in the genome gives a double helix roughly 2.2 metres long -- for comparison, E. coli's much smaller genome, with about 4.6 million base pairs, still stretches to around 1.36 millimetres, far larger than the roughly one-millionth-of-a-metre nucleus that a eukaryotic cell packs its DNA into. Solving this packaging problem is the subject of this section. Du Praw's 1965 'unineme' model proposed that eukaryotic DNA exists as a single, long, coiled molecule associated throughout its length with histone proteins, and plants and animals, having more DNA than bacteria, must fold it correspondingly more tightly to fit inside the nucleus. Prokaryotes such as E. coli, lacking a defined, membrane-bound nucleus altogether, nonetheless keep their DNA from scattering freely through the cell: because DNA is negatively charged, it is held compactly by association with positively charged proteins in a region called the nucleoid, organised into large loops anchored by protein; prokaryotic DNA is almost circular and, lacking the chromatin organisation eukaryotes use, is instead called a genophore. In eukaryotes the packaging system is considerably more elaborate. Roger Kornberg proposed the widely accepted nucleosome model, in which two copies each of four histone proteins, H2A, H2B, H3 and H4, assemble into a compact unit of eight molecules called a histone octamer; the negatively charged DNA then wraps almost twice around this positively charged octamer to form a single nucleosome, which typically contains about 200 base pairs of DNA. Successive histone octamers sit close together, with the DNA visibly coiling around the outside of each, while neighbouring nucleosomes are connected by short stretches of exposed linker DNA associated with a fifth histone, H1, which seals off the two turns of DNA around each octamer; chromatin lacking H1 shows a loose 'beads-on-a-string' appearance instead. H1 molecules from neighbouring nucleosomes can interact with each other, drawing the whole fibre into a further level of folding: a roughly 30 nanometre-diameter solenoid structure containing about six nucleosomes per turn, stabilised by these H1-H1 interactions, that packs the DNA by roughly …