Histone

Histones are basic proteins present in the cell nucleus of eukaryotic cells. They are available as part of the chromatin for the packaging of DNA (there are spools around which DNA winds ), but also for the expression of some genes encoded on their essential. In order to accommodate the large genome of eukaryotes in the nucleus, the DNA, it is necessary to pack special. In eukaryotes, this occurs in chromosomes whose smallest packaging unit is a nucleosome. A nucleosome is a " octamer ", it consists of eight histones: two copies of histones H2A, H2B, H3 and H4. DNA is wrapped around a 1.65 times nucleosome DNA which corresponds to a length of 146 base pairs. The non-associated DNA that connects adjacent nucleosomes is called linker DNA. The histone H1 binds DNA adjacent nucleosomes and allows the next higher packing unit of DNA.

Histone consist of a globular core and flexible terminal arms (English histone tails ) having many basic, ie positively charged amino acids. DNA is negatively charged, however, so that an electrostatic attraction is.

Discovery

The histone proteins were discovered in 1884 by German physician and physiologist Albrecht Kossel. The term histone can be derived from Greek histanai or histos. Until the early 90s histones were misinterpreted as pure packing material nuclear DNA. Only in the last two decades, its significance for the epigenetic mechanisms could be described.

Histonklassen

There are five main histone proteins known:

• H1
• H2A
• H2B
• H3
• H4

The histone H2A and H2B self-assemble into dimers. The same is true for H3 and H4. Two H3/H4-Dimere self-assemble into a tetramer, are attached to the turn two H2A/H2B-Dimere. This gives the octameric Nukleosomenkern (core particle ), around which the DNA can put in about two great left-handed turns. The fifth histone H1, may be required to form a 30- nm fiber - a higher-order structure, corresponding to a helix of the nucleosomes. Characterized the DNA package is further enhanced. The compression of the DNA molecule is not a factor of 7, and H1 will be increased by a factor 40-50 in H1, i.e., an uncompressed DNA strand comprising nucleotides 3 million / mm, compressed without H1 20 million nucleotides / mm, and 120 million nucleotides H1 / mm.

In addition to histone proteins mentioned above, there are also variants that take very specific functions in the regulation of gene expression and structure of the chromosomes. An example macro - H2A, which replaces the histone H2A partially on the inactivated X chromosome from female mammals. Another example is CENP -A, a variant of histone H3, which is found only in the region of the centromere and is essential for the specific structure of this chromosomal region. On the whole, the core histones H2A, H2B, H3 and H4 have been highly conserved in evolution. Only the histone H1 is highly variable in its structure, as the comparison of different organisms shows. In the baker's yeast ( Saccharomyces cerevisiae) histone this even completely missing. The binding of DNA to histones may affect the transcription positively or negatively. For the processes of transcription, replication and DNA repair histones must be released from the DNA or moved on the DNA strand - a process which is referred to as Nukleosomenremodelling.

Histone modifications

The N -terminus of a histone may be modified by enzymes. These histone modifications may include methylation, phosphorylation, sumoylation, ubiquitination, and acetylation and their reverse reactions. This results in the specific histone code of a cell. These modifications affect the chromatin of the nucleus and thus on gene regulation.

The function of the methylation of histones is currently being studied intensively and is mainly related to the epigenetic inactivation of genes. Thus, a regional trimethylation of lysine residue ( K9) on histone 3 lead a promoter to a condensation of the chromatin structure in this area, this then has an inactivation of the gene expression of the gene located on this section result. There are also links to the inactivating process of DNA methylation. Phosphorylation of histone proteins is increased in the majority of cases, the accessibility of DNA and plays an important role, inter alia, in the regulation of transcription during mitosis and meiosis. Is the acetylation, phosphorylation, such as, in most cases, the binding capacity of the histone to the DNA decreased by the charge of the histones is negative and the negative DNA repels. It is therefore a prerequisite for the transcription of the associated DNA with histones.

Histone

Histones are obviously evolutionarily very old and very important molecules, so that they are highly conserved. Histone genes are S- phase - dependent, so are only expressed when new DNA is formed, and then, although extremely strong.

The histone genes are similar to the rDNA repeats often occur in clusters before, are thus coupled, but they each have their own promoter. The number of repeats can vary quite strongly (Saccharomyces cerevisiae has two clusters, the Green newt has 700, in humans there are 10-24 ).

The order of the histone genes in the cluster is quite different, in part, the genes are also in opposite directions, partly arranged in the same direction. In each cluster, however, all five histones are present.

The histone genes themselves also have a downright ancient structure. You do not have introns, nor do they receive after transcription, a poly (A ) tail. The 3 ' UTR is very short and includes two oppositely directed repeating units ( inverted repeats ). These form a hairpin structure, which is otherwise known only from genes of prokaryotes. The hairpin structure is important for the coordinated maturation of histone mRNA and the regulation of their survival in the S phase.

In mammals and birds, the clusters are not repetitively arranged, but something distributed. Some histone genes are S phase - correlated and are quite close to each other. They correspond in structure to the "normal" Histongenen. Others, however, are so-called Ersatzhistongene intended to replace defective histone proteins, including those outside of S phase. These are off the Histoncluster and have long 3'- UTR and a poly (A ) tail.