Histone dimer

Richmond and collaborators (Figure 12.30). The octamer (Figure 12.29) has surface landmarks that guide the course of the DNA around the octamer 146 bp of B-DNA in a flat, left-handed superhelical conformation make 1.65 turns around the histone core (Figure 12.30), which itself is a protein superhelix consisting of a spiral array of the four histone dimers. Histone 1, a three-domain protein, serves to seal the ends of the DNA turns to the nucleosome core and to organize the additional 40 to 60 bp of DNA that link consecutive nucleo-... 

The core unit of the chromatin, the nucleosome, consists of histones arranged as an octamer consisting of a (H3/ H4)2-tetramer complexed with two histone H2A/H2B dimers. Accessibility to DNA-binding proteins (for replication, repair, or transcription) is achieved by posttranslational modifications of the amino-termini of the histones, the histone tails phosphorylation, acetylation, methylation, ubiquitination, and sumoyla-tion. Especially acetylation of histone tails has been linked to transcriptional activation, leading to weakened interaction of the core complexes with DNA and subsequently to decondensation of chromatin. In contrast, deacetylation leads to transcriptional repression. As mentioned above, transcriptional coactivators either possess HAT activity or recruit HATs. HDACs in turn act as corepressors. 

The state of the chromatin has influence as well on the velocity with which is produced the recognition between the receptor dimer and the HRE sequences. The inactive heterochromatin has methylated histones, so that a different... 

The structure of the chromatin and their state of acetylation are important at the moment of initiating the gene transcription. Indeed, some of the transcription factors recruited by the receptor dimer have histone-acetyltransferase activity that permits the gene transcription after diminishing the condensation of the chromatin (Gruber et al. 2002 Nilsson et al. 2001 Vigushin et al. 2002). 

The H2a-H2b histone dimer also has strong salt-dependent conformational properties, with a transition near 0.5 M NaCl.(93) Above 0.5 M NaCl, the tyrosine fluorescence emission becomes less quenchable by Cs+, and the dimer structure becomes more compact. 

Identification of Cross-Linked Histone Dimers and Trimers... 

Histone Dimer and Tetramer Obtained by Salt Dissociation... 

Specifically, when histones are dissociated from DNA in 2 M NaCl, and H3 H4 tetramer and H2A-H2B dimer may be identified after fractionation of the histones at pH 5.0 and cross-linking with dimethylsu-berimidate (Komberg and Thomas, 1974). The inference was drawn that these complexes exist as such in the intact nucleosome. Furthermore, since both the un-cross-linked H3 H4 tetramer, and the uncross-linked H2A-H2B dimer are stable complexes, it has proved possible to characterize their physical properties in solution. Some of these results are summarized here. 

As described in Section II,B, an H2A H2B-H4 trimer may be obtained by UV cross-linking of chromatin. Therefore, H2B apparently has two distinct binding sites for H2A and H4 (Martinson et al., 1979a). The lack of trimer formation by addition of a third histone to a preformed pair consequently must indicate that a trimeric unit is not stable. The dimer is the basic structural unit in the assembly of histones (Sperling and Bustin, 1976). This idea is supported by the fact that in a mixture of histones only even complexes have been isolated,... 

When the four core histones are mixed in equimolar ratio at low ionic strength a single sedimentation velocity peak is observed with Sjo.w = 2.0. Gel filtration and cross-linking with dimethylsuberimi-date showed that the peak contained a mixture of dimers (Sperling... 

Although the quantitation of the cross-linking data is limited, as discussed above, comparison of the cross-linked histones obtained from chromatin with histone complexes obtained in the absence of DNA can help in developing a more detailed picture of histone-histone interactions. An H2A-H2B dimer was obtained by cross-linking of chromatin with short-range cross-linkers (for references, see Section... 

The histone octamer is the histone unit of the nucleosome. As discussed in Section II, it has been shown that at high salt concentration (7 > 2 M) the core histones can assemble on their own, in the absence of DNA, to form histone octamers (this assembly occurs with both acid- and salt-extracted histones). Furthermore, the secondary and tertiary structures of core histones at high salt concentration are similar to the structures they have in the intact nucleosome. The basic units of the assembly of the four core histones are histone dimers which are obtained at low salt concentration. Upon increase in salt concentration, tetramers, hexamers, and octamers are obtained. The cross-linking pattern of histones in high salt concentration is similar to that in chromatin, again supporting the idea that the assembly of core histones at high salt concentration is similar to that in chromatin. 

In arrays of closely packed nucleosomes composed of all four core histones, strands of H2A-H2B dimers could be incorporated in the grooves between the two H3-H4 strands, producing a four-stranded polymer. Alternatively, they could bind to the H3-H4 double-stranded fiber to give an octamer of the histones per nucleosome. This latter model is supported by the photochemical cross-linking of histones to DNA which have shown that within the nucleosome core the four core histones are not equivalently positioned with respect to... 

Covalent links of histones HI, H2A, H2B, and H3 with poly(ADP-ribose) have been reported (for references, see Hayaishi and Ueda, 1977). Furthermore, a histone HI dimer linked by poly(ADP-ribose) has been reported. The increase in ADP-ribosylation is concomitant with cellular replication and ADP-ribosylation has been proposed as a trigger for in vivo replication in eukaryotic cells. 

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