Chromatin DNA model

Fig. 5. Solenoid model of the 30-nm filament of chromatin, where the disks represent nucleosomes and the dark line unbound DNA.

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

Recently, a low-resolution model of the chromatin core particle has been derived from a combination of single-crystal X-ray diffraction and electron microscopic data (Finch et al., 1977). The particle is described as a flat cylinder 110 A in diameter and 57 A in height. A similar shape and similar dimensions were found to be consistent with the low-angle neutron scattering from core particles in solution (Pardon et al., 1977 Suau et al., 1977). Some conclusions may be drawn concerning the conformation of the DNA. Presumably, the strong 28 A periodicity apparent in the crystal data (Finch et al., 1977) corresponds to the pitch of the DNA superhelix wound about the histone core. X-Ray and spectroscopic data suggest that the DNA super-... 

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.)...

Simpson RT, Thoma F, Brubaker JM (1985) Chromatin reconstituted from tandemly repeated cloned DNA fragments and core histones a model system for study of higher order structure. Cell 42 799-808 Sugiyama S, Yoshino T, Kanahara H, Kobori T, Ohtani T (2003) Atomic force microscopic imaging of 30 nm chromatin fiber from partially relaxed plant chromosomes. Scanning 25 132-136 Sugiyama S, Yoshino T, Kanahara H, Shichiri M, Fukushi D, Ohtani T (2004) Effects of acetic acid treatment on plant chromosome structures analyzed by atomic force microscopy. Anal Biochem 324 39 4... 

Erard M, Lakhdar-Ghazal F, Amalric F (1990) Repeat peptide motifs which contain beta-turns and modulate DNA condensation in chromatin. Eur J Biochem 191 19—26 Erard MS, Belenguer P, Caizergues-Ferrer M, Pantaloni A, Amalric F (1988) A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone HI. Eur J Biochem 175 525—530 Falaschi A (2000) Eukaryotic DNA replication a model for a fixed double replisome. Trends Genet 16 88-92... 

Aureolic acid group of antibiotics We have given below an extended summary of the work done with this group of antibiotics, because we have been actively involved in understanding the mode of action of these DNA-binding antibiotics. The summary also illustrates the model example of how different biophysical and biochemical approaches were undertaken to characterize the association of these drugs with chromosomal DNA and the sequential effect of this binding upon the chromatin structure. 

Two approaches are usually taken to study the effect of the association of DNA binding anticancer drugs upon the structure of chromatin and nucleosome. The first one is reconstitution of the model nucleosome in the presence of the drugs. This has been reported earlier in the case of mithramycin (Fox and Cons, 1993 Carpenter et al., 1993). In our laboratory, so far we have taken the second approach of comparing the association of the anticancer drugs with isolated chromatin at various levels. 

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