Histone modification
Histone modifications are chemical changes in histone proteins that, among other things, have an impact on transcription .
Types of modifications
Histone modifications were found both at the unstructured N- and C-terminal ends of the histone proteins and in the globular area within the nucleosome core.
nomenclature
The following nomenclature has been developed to denote histone modifications:
- The name of the histone (e.g. H3)
- The affected amino acid in its one -letter code (e.g. K for lysine ) with the position of the amino acid in the protein
- The type of modification (me: methyl , P: phosphate , Ac: acetyl , Ub: ubiquitin )
- In the case of methylation, the number of methyl groups (for lysines and arginines ) and the symmetry (for dimethylated arginines) can also be specified.
Examples:
- Trimethylation of the lysine at position 4 of histone 3: H3K4me3
- symmetrical methylation of arginine 8 at histone 3: H3R8me2s
- Acetylation of the lysine at position 20 on histone 4: H4K20Ac
Acetylation
Histone acetylation takes place exclusively on lysines (e.g. H3K9Ac, H3K27Ac, H4K16Ac, H4K20Ac). The main effect of the acetyl group is to neutralize the positive charge of the 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 30 nm fiber (solenoid structure), which allows the binding of transcription factors and the transcription machinery, thus promoting transcription. Histone acetylations are generated by histone acetyltransferases (HAT) and removed again by histone deacetylases (e.g. HDAC4 ).
Methylation
Histone methylation is found on both lysines and arginines. Histone methylation can correlate positively as well as negatively with transcription, depending on which lysine / arginine one is looking at. Lysines can also be modified with one, two or three and arginines with up to two methyl groups. These different methylation states are often distributed differently in the genome and therefore probably also have different biological functions. Histone methylation is generated by histone methyltransferases (HMT) and removed by histone demethylases (HDM).
Important methylations are:
- H3K4me2 / 3 (found on the promoters of actively transcribed genes )
- H3K27me3 (found on repressed genes)
- H3K9me3 (found in heterochromatin )
- H3K4me1 / 2 (can be found in active enhancers )
- H3K36me3, H4K20me1 (found in the gene body of actively transcribed genes)
Phosphorylation
Histone phosphorylation can take place on amino acids with a hydroxyl group , i.e. on serines , threonines and tyrosines . Histone phosphorylations are as diverse in their function as histone methylations.
Other known modifications
- Propionylation
- Butyrylation
- Ubiquitinylation
- ADP ribosylation
- Sumoylation
- Carbonylation
- Glycosylation
- Biotinylation
- cis-trans isomerization on prolines
- Citrullination on arginines
Histone code
In addition to the direct influence on the chromatin structure, such as acetylation, many histone modifications appear to have only an indirect influence on biological processes. The discovery of a large number of proteins that can recognize certain histone modifications (especially methylations) ("histone readers") lead to the conclusion that many modifications serve as binding sites for proteins that translate the information into subsequent processes. Since each nucleosome has a large number of potential modification sites, and these in turn can have several different modifications (e.g. a lysine can be unmodified, acetylated, mono-, di- or trimethylated), a single nucleosome can have an enormous number of different combinations have. In this context, one speaks of the histone code hypothesis . The hypothesis states that the combination of different histone modifications can be read off by binding proteins and their interaction leads to certain biological processes. The correctness of this hypothesis is currently the subject of intense discussion.
| Histone | modification | Heterochromatin | Euchromatin | Combinatorics and Consequences |
|---|---|---|---|---|
| H3 | Lys4me | + | ||
| H3 | Lys9me (1-3) | + | HP1 - (PcG) bond; promotes DNAme, inhibits Ser10p, generally inhibits Lys-ac | |
| H3 | Lys-ac | + | ||
| H3 | Ser10p | (+) | (+) | inhibits lyses and others; promotes Lys9, 14ac and vice versa |
| H3 | Lys14ac | |||
| H3 | Lys27me | |||
| H3 | Lys36me | |||
| H4 | Arg3me | + | EsaI bond; promotes Lys5ac and vice versa | |
| H4 | Lys5ac | |||
| H4 | Lys12ac | + | ||
| H4 | Lys16ac | promotes His18p and vice versa | ||
| H4 | His18p | inhibits Lys20me | ||
| H4 | Lys20me | promotes Lys16ac |
- ↑ For the meaning of the abbreviations, see nomenclature .
- ↑ PcG: Polycomb Group Protein
- ↑ Where “+” symbols are in brackets, the effect depends on the combinations of various modifications
- ↑ Esa1: Acetyltransferase, an activating enzyme
The interaction of histones and DNA is controlled by histone modifications. These modifications can change the chromatin structure and thus lead to changes in gene activity . These epigenetic mechanisms can thus influence the transcription of individual genes or entire groups of genes.
swell
- T. Jenuwein, CD Allis : Translating the Histone Code In: Science. 293 (5532), 2001, pp. 1074-1080. PMID 11498575
- BD Strahl, CD Allis: The language of covalent histone modifications. In: Nature. 403 (6765), 2000, pp. 41-45. PMID 10638745