The Nucleosome Contains Histone DNA

When the histone octamer is mixed with purified, double-stranded DNA, the same x-ray diffraction pattern is formed as that observed in freshly isolated chromatin. Electron microscopic studies confirm the existence of reconstituted nucleosomes. Furthermore, the reconstitution of nucleosomes from DNA and histones H2A, H2B, H3, and H4 is independent of the organismal or cellular origin of the various components. The histone H1 and the nonhistone proteins are not necessary for the reconstitution of the nucleosome core.

Table 36-1. Possible roles of modified histones.

1. Acetylation of histones H3 and H4 is associated with the activation or inactivation of gene transcription (Chapter 37).

2. Acetylation of core histones is associated with chromosomal assembly during DNA replication.

3. Phosphorylation of histone H1 is associated with the condensation of chromosomes during the replication cycle.

4. ADP-ribosylation of histones is associated with DNA repair.

5. Methylation of histones is correlated with activation and repression of gene transcription.

In the nucleosome, the DNA is supercoiled in a left-handed helix over the surface of the disk-shaped histone octamer (Figure 36-2). The majority of core histone proteins interact with the DNA on the inside of the su-percoil without protruding, though the amino terminal tails of all the histones probably protrude outside of this structure and are available for regulatory covalent modifications (see Table 36-1).

The (H3/H4)2 tetramer itself can confer nucleo-some-like properties on DNA and thus has a central role in the formation of the nucleosome. The addition of two H2A-H2B dimers stabilizes the primary particle and firmly binds two additional half-turns of DNA previously bound only loosely to the (H3/H4)2. Thus, 1.75 superhelical turns of DNA are wrapped around the surface of the histone octamer, protecting 146 base pairs of DNA and forming the nucleosome core particle (Figure 36-2). The core particles are separated by an about 30-bp linker region of DNA. Most of the DNA is in a repeating series of these structures, giving the so-called "beads-on-a-string" appearance when examined by electron microscopy (see Figure 36-1).

The assembly of nucleosomes is mediated by one of several chromatin assembly factors facilitated by histone chaperones, proteins such as the anionic nuclear protein nucleoplasmin. As the nucleosome is assembled, his-tones are released from the histone chaperones. Nucleo-somes appear to exhibit preference for certain regions on specific DNA molecules, but the basis for this nonran-dom distribution, termed phasing, is not completely

Figure 36-2. Model for the structure of the nucleosome, in which DNA is wrapped around the surface of a flat protein cylinder consisting of two each of histones H2A, H2B, H3, and H4 that form the histone octamer. The 146 base pairs of DNA, consisting of 1.75 superhelical turns, are in contact with the histone octamer. This protects the DNA from digestion by a nuclease. The position of histone H1, when it is present, is indicated by the dashed outline at the bottom of the figure.

Figure 36-2. Model for the structure of the nucleosome, in which DNA is wrapped around the surface of a flat protein cylinder consisting of two each of histones H2A, H2B, H3, and H4 that form the histone octamer. The 146 base pairs of DNA, consisting of 1.75 superhelical turns, are in contact with the histone octamer. This protects the DNA from digestion by a nuclease. The position of histone H1, when it is present, is indicated by the dashed outline at the bottom of the figure.

understood. It is probably related to the relative physical flexibility of certain nucleotide sequences that are able to accommodate the regions of kinking within the super-coil as well as the presence of other DNA-bound factors that limit the sites of nucleosome deposition.

The super-packing of nucleosomes in nuclei is seemingly dependent upon the interaction of the H1 his-tones with adjacent nucleosomes.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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