Chromatin refers to the complex of DNA and thousands of proteins that make up the chromosomal axes. With regards to eukaryotic DNA, cells have 2 main problems:
The answer to these problems is chromatin which enables a large amount of DNA to become highly condensed, while also making DNA accessible to important proteins (such as transcription factors) by the highly flexible structure of some regions of the chromatin. Thus, chromatin is a combination of nuclear DNA and proteins allowing continuous accessibility of genes in the cell nucleus.
The nucleosomal 10nm fiber is often referred to as 'beads on a string' owing to its appearance under the electron microscopy. It is also known as being the primary level of chromatin organization. The nucleosomes (i.e. the beads) are made up approximately 147 base pairs of DNA wrapped around a core histone octamer. The histone octamer is made up of two copies of each of the histones H2A, H2B, H3 and H4. The N-terminal tails of H2B and H3 pass through the two DNA strands wrapped around them, and can undergo covalent modifications. The nucleosomes are linked together by linker DNA of variable lengths forming the string. The structure of the core nucleosome is well conserved (highlighting its importance), other than the linker region of DNA that can be variable in length.
Compaction in the form of the 10nm nucleosomal fiber could be very restricting upon DNA accessibility, thus nucleosome structure is susceptible to modification. These modifications can include:
The above factors have been proven as the key to regulate the dynamics of the nucleosome and the correct spatial and temporal accessibility of the DNA.
The 30nm fiber is known as the secondary structural level of chromatin. The histone H1 is thought to be involved in the promotion and formation of the 30nm fiber. This can be shown in nucleosomes lacking H1 which do not readily form the 30nm fiber. Histone H1 is also known as the linker histone, due to its association with the linker DNA between nucleosomes. However, unlike the 10nm fiber the exact structure of the 30nm fiber remains still to be resolved because the structure is too compact for us to visualise the spatial arrangement of the nucleosomes. It is also hard to structurally characterise as the native chromatin is very heterogeneous, being made up of different DNA sequences and different histone variants and modifications. There are currently two different models for the 30nm fiber:
Currently results from electron microscopy and analysis of crystal structures favour the Zig-Zag model.
Higher order chromatin is polymorphic in its structure, and it is still unclear as to whether there is a definite hierarchical set of structures above the 30nm fiber. The mitotic chromosome is an obvious example of higher order structure. Light and electron microscopy, plus newer immunogold labelling techniques have uncovered banding patterns of chromatin, with untranscribed gene deserts more tightly compacted compared to gene rich areas. There is little sound evidence for a conserved higher order structure, but below are some examples.
A consistent example of higher order chromatin structure is the mitotic metaphase chromosome. However, little is known about its organization. In the metaphase chromosome DNA is compacted 10,000-20,000 fold. For any given species the arm dimension of the metaphase chromosome remains constant, independent of the DNA sequence associated with it.
The core structures of higher order chromatin are chromosome scaffolds. The chromosome scaffold is made up of two primary components:
Attached to the scaffolds are chromatin loops. These loops are connected to the chromosome scaffolds via SARs (scaffold associated regions). SARs are AT (Adenine/ Thymine) rich regions of the chromosome scaffold that unfold more readily (possibly facilitating the access of factors required for DNA processes). AT-queue regions are formed by the arrangement of the SARs along the chromosome scaffold, with relatively tight folding in some areas and more unfolded in others.
Evidence for the chromosome scaffold can also be seen in lampbrush chromosomes (LBC's). LBC's are generally confined to meiosis in oocytes. They are large with a linear chromosome axis with large loops emerging from them. Each loop is rich in actively expressed genes (transcriptional units) suggesting LBC's are an adaptation to maximize transcriptional output in oocytes. However, the majority of the DNA (mostly non-expressed genes) is still found condensed at the chromosome axis.
Epigenetics is the study of inherited changes caused by mechanisms other than changes in DNA sequence. Human disorders such as Prader-Willi syndrome are known to have been caused by epigenetic changes. Chromatin component changes such as in histone variants, chromatin re-modelling factors and histone modifications can produce these effects. Sometimes chromatin components can be sensitive to environmental and metabolic circumstances that alter gene expression. This altered gene expression is heritable in cells, and if such occur in germ cells they can be passed onto the offspring.
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Becker (2009) The world of the cell; Seventh edition;chapter 18: pages 534-544
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