Histone code

Histone modifications are chemical modifications on histone proteins that affect the others on transcription.

Types of modifications

Histone were found both in the unstructured N-and C -terminal tails of histone proteins and in the globular area within the nucleosome core.

Nomenclature

To identify histone modifications, the following nomenclature has developed:

Examples:

  • Trimethylation of lysine at position 4 of the histone 3: H3K4me3
  • Symmetrical methylation of arginine 8 on histone 3: H3R8me2s
  • Acetylation of lysine at position 20 on histone 4: H4K20Ac

Acetylation

Histone acetylation takes place exclusively at lysines (eg, H3K9Ac, H3K27Ac, H4K16Ac, H4K20Ac ). The main effect of the acetyl group is to neutralize the positive charge of lysine. The consequence is a reduction in the electrostatic interaction between the lysine and the negative charges on the DNA. This leads to an opening of the chromatin structure, which allows the binding of transcription factors and the transcription machinery, and so promotes transcription. Histone acetylation generated by histone acetyltransferases (HAT) and removed by histone deacetylases (HDAC ).

Methylation

Histone methylation can be found both at lysines and arginines at. Histone methylation can correlate both positively and negatively with transcription, depending on which lysine / arginine is considered. Lysine also with one, two or three, and arginine may also be modified with up to two methyl groups. These different methylation states are often unevenly distributed in the genome and therefore probably also have different biological functions. Histone methylation is generated by histone methyltransferases (HMT ) and removed by histone demethylases ( KDM).

Important methylations are:

  • H3K4me2 / 3 ( can be found at the promoters of actively transcribed genes as well as to unmethylated CpG islands )
  • H3K27me3 ( can be found at repressed genes )
  • H3K9me3 ( can be found in heterochromatin )
  • H3K4me1 / 2 ( can be found in active enhancers )
  • H3K36me3, H4K20me1 ( can be found in the gene body of actively transcribed genes )

Phosphorylation

Histone phosphorylation may occur at amino acids with a hydroxyl group, that is to serines, threonines, and tyrosines. Histone phosphorylation are similar diverse as histone methylations in their function.

Other well-known modifications

  • Ubiquitination
  • ADP-ribosylation
  • Sumoylation
  • Carbonylation
  • Glycosylation
  • Biotinylation
  • Cis -trans isomerization of proline residues

Histone code

In addition to the direct effect on the chromatin structure, such as by acetylation, many histone modifications appear only indirectly influence biological processes to have. Can recognize the discovery of a number of proteins, the specific histone modifications (in particular methylation ) ( " Histone Reader" ), it can be concluded that many modifications serve as a binding site for proteins that translate the information in subsequent processes. Since each nucleosome having a large number of potential modification sites, and this in turn may have a plurality of different modifications ( for example, a lysine can be unmodified, acetylated, be mono-, di-or Trimethylated ), a single nucleosome can have a tremendous number of different combinations. One speaks in this context of the histone code hypothesis. The hypothesis is that the combination of different histone modifications read by binding proteins and their interaction results in specific biological processes. The correctness of this hypothesis is currently the subject of intense discussion.

The interaction of histones and DNA is controlled by histone modifications. These modifications can alter the chromatin structure and thus lead to changes in gene activity. Thus, this epigenetic mechanisms can affect the transcription of individual genes or groups of genes.

Swell

  • Jenuwein T, Allis CD (2001) Translating the histone code In: Science. 293 (5532) :1074 - 1080th PMID 11498575
  • Ray BD, Allis CD ( 2000): The language of covalent histone Modifications. In: Nature. 403 (6765) :41 - 45th PMID 10638745
  • Chromatin
  • Epigenetics
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