Chromatin fiber histone acetylation

In summary what have we learned in 25 years In some areas, surprisingly little— for example, we cannot say that we really understand the condensed chromatin fiber structure much better than we did in 1978. Although the significance of the great majority of histone variants remains unknown, replacement histones appear now to be involved in major chromosomal functions. There are areas in which we have accrued incredible amounts of detailed information yet still do not quite know what to do with it. Histone acetylation is a prime example. Allfrey et al. [56] could predict its role in a general sense in 1964. We now know a whole rogue s gallery of acetylases and deacetylases plus the specific histone sites for many. Nevertheless, authorities in the field must still write in 2000, The mechanisms by which histone acetylation affects chromatin structure and transcription is not yet clear [58]. 

Experimental results regarding the role of the histone tails indicate that these histone domains play a critical role in chromatin folding [358,365]. Removal as well as the modification (acetylation) of the lysine amino acids within these regions produces an imbalance of the electrostatic interactions, which results in a hierarchically impaired folding ability (H3/H4-H2A/H2B>H3/H4>H2A/H2B) of the chromatin fiber [358,366-369]. Therefore, sources of histone tail variability (histone variants and post-translational modifications other than lysine acetylation) are also likely to alter the extent of folding of chromatin. 

Histone acetylation is without a doubt one of the most thoroughly characterized post-translational modifications of histones where both the functional (see Section 3.1) and structural implications for chromatin have been explored. In the sections that follow we are going to summarize the major structural effects of this post-translational modification as they pertain to the nucleosome and the chromatin fiber. 

The major structural effects of histone acetylation that affect both the nucleosome core particle and the chromatin fiber are schematically summarized in Fig. 13. 

Isolated di- and trinucleosomes Hyper-acetylated CE chromatin fibers isolated in the presences of the histone deacetylase inhibitor sodium butyrate... 

Figure 1. Hierarchical model of chromosome structure, (a) In interphase cells, DNA is packed in a nucleus as forming nucleosome and chromatin, (b) DNA forms nucleosome structure together with core histone octamer, which is then folded up into 30nm fiber with a help of linker histone HI. This 30 nm fiber is further folded into 80 nm fiber and 300 nm loop structures in a nucleus. In mitosis, chromosome is highly condensed. Proteins which are involved in each folding step are indicated above and non-protein factors are indicated below, (c) The amino acid sequences of histone tails (H2A, H2B, H3 and H4) are shown to indicate acetylation, methylation and phosphorylation sites. (See Colour Plate 1.)...

Each of the histone proteins making up the nucleosome core contains a flexible amino terminus of 11-37 residues extending from the fixed structure of the nucleosome these termini are called histone tails. Each H2A also contains a flexible C-termlnal tall (see Figure 10-20b). The histone tails are required for chromatin to condense from the beads-on-a-string conformation Into the 30-nm fiber. Several positively charged lysine side chains In the histone tails may interact with linker DNA, and the tails of one nucleosome likely interact with neighboring nucleosomes. The histone tail lysines, especially those In H3 and H4, undergo reversible acetylation and deacetylation by enzymes that act on specific lysines In the N-termlnl. In the acetylated form, the positive... 

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