The histones are basic Protéines in close contact with DNA. To date, five histones are described:
- histones H2A, H2B, H3 and H4 form a globular Octamère (of structure 2x (H2A, H2B, H3, H4)) who allows the rolling up of 146 pairs of bases of DNA in a turn three quarter in order to form a Nucléosome;
- the histone H1 allows as for it the compaction of the Nucléosome S and rigidifies the helicoid structure thus obtained. Contrary to several ARNm, the histones do not have a tail poly-a.
The degree of condensation of the DNA around the nucléosomes of histones and of proteins not histone is variable along the chromosomes. It is weak in the Euchromatine which one says “open” and accessible to the machinery from ARN polymerase S. It is high in the Hétérochromatine, that one says “closed” and “inaccessible” to the machinery of transcription.
This degree of condensation is babbit metal by modification of the N-final ends of the histones, like Phosphorylation S, Acétylation S, Méthylation S, Ubiquitination S, Sumoylation S, etc the whole of these modifications being catalyzed by specific enzymes. The covalent modifications of the histones would act either directly by modifying the compaction of the rolling up of DNA around the nucléosomes, or indirectly by constituting “marks” allowing the protein recruitment able to modify the structure of the Chromatine. The acting model of the covalent modifications of the histones as a code (the “code of the histones”) was proposed by Strahl and Allis in 2000 in the review Nature . One can however note that this code is, seems it, far from being universal, but rather relatively specific according to genes and the cells considered.
In the Spermatozoon S, the histones are replaced by Protamine S, proteins rich in Arginine and Cystéine. The high content in cystein allows the formation of Pont disulfide. This structure protects the DNA at the time of possible Déplacement S related to the Fécondation.
the code of Histones
The code of the histones draws up a direct link between the modification of certain residues of the tail of the histones which created connections for effector proteinic and the state transcriptionnel of chromatin. A modification of histone can influence another of them in a synergistic or antagonistic way; it is a mechanism which generates and stabilizes specific prints. Acetylation (addition of grouping acétyl) is carried out on certain residues lysin precis by named enzymes histones acétyl transférases (HAT). It generally decreases the interaction inter-nucléosomes and between the tails of the histones and the fragment of DNA which establishes the link between the nucléosomes. This involves the relaxation of chromatin, making it pass to the state euchromatinien, and thus allows a better accessibility the other factors. Acetylation is associated with an activation of the transcription and is easily reversible thanks to the action of the histones désacétylases (HDAC).
The methylation, as for it, can be carried out either on lysins or on arginines. It is a stable modification and hitherto very few histones déméthylases was discovered. According to the methylated residues it is associated with an activation or a repression of the transcription.
In a general way, these two types of modifications are antagonistic, and the desacetylation of lysins must precede their methylation. This antagonism involves the installation of a certain dynamic balance between the territories hétérochromatiniens (generally not exprimables and methylated on certain key amino-acids) and euchromatiniens (generally exprimables and acetylated). For example, Lysin 9 of the histone H3 is known to be associated with a repression with surrounding chromatin when it is methylated. This methylation is recognized by proteins, HP1, which is thus fixed on H3 methylated. In its turn, HP1 attracts the protein Suv39, Histone MethylTransférase, which will be able méthyler lysin 9 of the histone H3 of the close nucléosome, and so on. One thus sees, how, gradually, the histones H3 will be methylated and chromatins will be condensed. however, this invasion hétérochromatinienne will be stopped if lysin 9 of H3 met is already Acétylée. Thus a competitive balance between chromatiniens field is set up expressed and repressed.
The modifications of the tails of histones play the part of epigenetic “marks” which involve the recruitment of various protein classes, since acetylated or methylated lysins are recognized by different proteinic fields. Moreover, the recruitment of certain factors on the level of chromatin requires the preliminary existence of modifications of histones and already dependant proteins. The code of the histones is thus interpreted in the context of other factors associated with chromatin and it is the combination of interaction between the modified histones and other factors which determines if a protein is recruited with chromatin.
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