Histones Amino acid sequence

Fig. 4. Amino acid sequence of several histone HI proteins to illustrate the macroheterogeneity of linker histones. Amino acid sequence of two highly specialized development-specific members of the histone HI family. A. Oocyte specific mammalian histone Hlfo (previously Hloo) [116]. B. PL-I (EM-1/6) protein from the sperm of the razor clam Ensis minor [120]. These two sequences are shown in comparison to the highly specialized histone H5 from chicken erythrocytes. The regions corresponding to the trypsin-resistant (winged helix motif [96]) which is characteristic of the protein members of the histone HI family are indicated by a box and have been aligned to show the sequence similarity.

Charge neutralization. Given the histone amino acid sequences illustrated below, estimate the charge of a histone octamer at pH... 

Fic. 1. The amino acid sequences of calf histones H2A (Yeoman et al., 1972 Sau-tiere et al., 1974) and H2B (Iwai et al., 1972). A one-letter code is used A, alanine R, arginine N, asparagine D, aspartic acid C, cysteine E, glutamic acid Q, glutamine ... 

Fig. 2. The amino acid sequencies of calf histone H4 (DeLange et al., 1972 Ogawa et al, 1969) and H3 (DeLange et al., 1972 Olson et al., 1972 DeLange et al., 1973). The notation is as in Fig. 1 except that superscript M denotes methylation site.

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.)...

Figure 2. Histone H2A variants from yeast Saccharomyces cerevisiae S.c.), fruit fly Drosophila melanogaster D.m ), and human Homo sapiens H.s.). Two conserved domains distinguish H2A.Z-relatives (boxed regions amino acid sequences in the top). H2A.X possesses a conserved C-terminal stretch of four amino acids. The serine (red) becomes phosphorylated at sites of DNA damage. H2A ( Barr body-deficient ) and marcoH2A are present in mammals...

H2A Barr body-deficient (Bbd) is an evolutionary relatively young histone variant sharing only about 48% amino acid sequence similarity to H2A. This histone variant appears to be specific for mammals (Chadwick and Willard 2001). As indicated by the name, the transcriptionally inactive and highly condensed X chromosome in female mammals (also known as Barr body ) is depleted for H2A , while this variant is detectable in autosomes and the active sex chromosomes. This observation suggested that H2A is linked to transcriptionally active euchromatin. H2A cofractionates in sedimentation centrifugation with hyper-acetylated histone H4, further corroborating that it associates with transcriptionally active euchromatin. 

Fig. 1. Core histone modifications. Human histone N-terminal and in some cases C-terminal amino acid sequences are shown. The modifications include methylation (M), acetylation (Ac), phosphorylation (P), ubiquitination (U), and ADP ribosylation (step ladder). The sites of trypsin digestion of histones in nucleosomes are indicated (T).

Fig. 1. Amino acid sequence of several representative homomorphous human core histone variants [12] A. Histone H2A B. Histone H2B C. Histone H3 and D. histone H4 variants. The amino acid residues are shaded with intensity proportional to the extent of identity shared among the compared sequences.

Found in the chromatin of all eukaryotic cells, histones have molecular weights between 11,000 and 21,000 and are very rich in the basic amino acids arginine and lysine (together these make up about one-fourth of the amino acid residues). All eukaryotic cells have five major classes of histones, differing in molecular weight and amino acid composition (Table 24-3). The H3 histones are nearly identical in amino acid sequence in all eukaryotes, as are the H4 histones, suggesting strict conservation of their functions. For example, only 2 of 102 amino acid residues differ between the H4 histone molecules of peas and cows, and only 8 differ between the H4 histones of humans and yeast. Histones HI, H2A, and H2B show less sequence similarity among eukaryotic species. 

All of the core histones share a conserved 65-residue histone fold.27 28 The arginine-rich histones have a strongly conserved amino acid sequence, histone H4 from pea seedlings differing from that of the bovine thymus by only two amino acids. On the other hand, the lysine-rich HI is almost species-specific in its sequence. Differentiated tissues contain at least seven variant forms of histone HI including proteins designated HI0, Hit, and H5 29-31... 

The chromosomal DNA is complexed with five types of histone (HI, H2A, H2B, H3 and H4). These are very basic proteins, rich in arginine and lysine. The amino acid sequences of histones are highly conserved in evolution. The DNA is wound round a histone octamer (two molecules each of H2A, H2B, H3 and H4) to form a nucleosome. The DNA between neighboring nucleosomes (linker DNA) binds histone HI. The packing ratio of nucleosomes is about 7. 

The DNA forms a left-handed superhelix as it wraps around the outside of the histone octamer. The protein core forms contacts with the inner surface of the superhelix at many points, particularly along the phosphodiester backbone and the minor groove of the DNA. Nucleosomes will form on almost all DNA sites, although some sequences are preferred because the dinucleotide steps are properly spaced to favor bending around the histone core. Histone HI, which has a different structure from the other histones, seals off the nucleosome at the location at which the linker DNA enters and leaves the nucleosome. The amino acid sequences of histones, including their amino- terminal tails, are remarkably... 

A general role for HU/HTa proteins in DNA packaging is not clear these proteins are not related to eukaryotic histones in terms of amino-acid sequence similarity (see Fig. 2) and they form pseudo-nucleosomes in vitro whose structure is still controversial [40-42]. HTa tetramers condense the DNA into small particles of 5.5 nm, which is only half... 

The amino acid sequences of four histones (H2A, H2B, H3, and H4) are remarkably similar among distantly related species. For example, the sequences of histone F13 from sea urchin tissue and calf thymus differ by only a single amino acid, and H3 from the garden pea and calf thymus differ only In four amino acids. Minor histone variants encoded by genes that differ from the highly conserved major types also exist, particularly in vertebrates. 

The amino acid sequence of HI varies more from organism to organism than do the sequences of the other major histones. In certain tissues, HI is replaced by special histones. For example, in the nucleated red blood cells of birds, a histone termed H5 is present in place of HI. The similarity In sequence among histones from all eukaryotes suggests that they fold into very similar three-dimensional conformations, which were optimized for histone function early in evolution in a common ancestor of all modern eukaryotes. 

Except for histone H4, each histone exists in several closely related subfractions or variants that have slightly different amino-acid sequences. Different tissues have different proportions of the various subfractions, but it is not known if this tissue specificity has functional significance. A substantial variant of histone HI, termed H10, has... 

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