In the eukaryotic cell, the structure of each chromosome is highly ordered. To achieve this, the large, negatively-charged nuclear DNA molecules are bound by various proteins, including both positively-charged, highly-conserved histone proteins and also non histone proteins. The DNA–protein complex is often described as chromatin, but certain noncoding RNAs can be intimately associated with chromosomal DNA too.
The greatest constraint on chromosome structure occurs when cells prepare to divide—the immensely long chromosomal DNA molecules must be very carefully pack aged so that they do not get tangled during cell division. At metaphase, therefore, the chromosomes are extremely condensed: their linear size is about 0.01% of the length of the fully extended chromosomal DNA. Metaphase chromosomes have a protein scaffold that contains high amounts of certain non histone proteins, including topoisomerase II and protein complexes known as condensins. Condensins organize tight packaging of the chromatin, and they have been imagined to bring together distant regions of the DNA, possibly by enclosing them in ring structures, but the exact mechanism is presently unclear.
At interphase, the long part of the cell cycle that occurs between successive mitoses, the DNA is in a very highly-extended form. Nevertheless, the 2 nm thick DNA double helix is compacted to a small degree. A first level of DNA packaging involves periodic coiling of the double helix round a complex of histone proteins. The nucleosome has a core DNA region, uniformly 146 base pairs (bp) in length, that is wrapped around eight histone proteins (two molecules each of four core histones; Figure 1A and B). Adjacent nucleosomes are connected by a short stretch of linker DNA that can be as long as 114 bp (but varies between species) in transcriptionally active (“open”) chromatin. A fifth type of histone, histone H1, binds to the linker DNA close to the nucleosome (see Figure 1A and B). Electron micrographs of suitable preparations show nucleosome filaments to have a “string-of-beads” appearance (Figure 1C).
Fig1. Nucleosome organization as a key step in compacting DNA in eukaryotic cells. (A) Binding of basic histone proteins causes the 2 nm thick DNA double helix to undergo a first level of compaction. The key structure is the nucleosome, a stretch of 146 bp of DNA wrapped in almost two turns around eight core histone proteins: two each of histones H2A, H2B, H3, and H4. A further histone, H1, is bound to linker DNA immediately outside the nucleosome; it seems to keep in place the DNA wrapped round the nucleosome. (B) Nucleosome detail. Left, a magnified view of a nucleosome. Right, the extensive α-helical structure of the core histones and their protruding N-terminal tails (note that many of the amino acids of the N-terminal tails are chemically modified, notably by methylation, acetylation, or phosphorylation, but are not shown here). (C) Electron micrograph of nucleosomal filaments showing the classic “beads-on-a-string” structure.
The N-terminal tails of the core histones protrude from the nucleosomes (Figure 1B). Specific amino acids in the histone tails can undergo various types of post-translational modification, notably acetylation, phosphorylation, and methylation, and so on. As a result, different proteins can be bound to the chromatin in a way that affects how the chromatin is packed and the local level of transcriptional activity. Additional histone genes encode variant forms of the core histones that may be associated with specialized functions and particular chromosomal regions, such as centromeres (see below).
