Nucleosome structure

Finally, the binding of specific transcription factors to cognate DNA elements may result in disruption of nucleosomal structure. Many eukaryotic genes have multiple protein-binding DNA elements. The serial binding of transcription factors to these elements—in a combinatorial fashion—may either directly disrupt the structure of the nucleosome or prevent its re-formation or recruit, via protein-protein interactions, multiprotein coactivator complexes that have the ability to covalently modify or remodel nucleosomes. These reactions result in chromatin-level structural changes that in the end increase DNA accessibifity to other factors and the transcription machinery. 

Cocco, L., Martelli, A., Billi, A., Matteucci, A., Vitale, M., Neri, L., and Manzoli, F. (1986) Changes in nucleosome structure and histone H3 accessibility. Iodoacetamidofluorescein labeling after treatment with phosphatidylserine vesicles. Exp. Cell Res. 166, 465 174. 

The Beato group has studied in depth the influence of the nucleosome structure in response to glucocorticoids (Beato 1989). Nucleosomes are formed by segments of 120 nucleotides of the double helix of DNA that make two twists around an octamer of histone. There are 200 nucleotides between two consecutive nucleosomes, so that a gene normally has tens of nucleosomes. 

It is interesting to note that nucleohistone lacking amino termini does not aggregate as readily in the presence of MgCl as do untreated particles (Whitlock and Stein, 1978). It might be hypothesized from this result that, although the amino termini are not necessary for the maintenance of nucleosome structure, they are involved in vivo in in-temucleosomal interactions. 

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.)...

During the cell cycle, chromosome structures shuttle between de-condensed interphase and condensed mitosis states. Dynamic changes also occur at the lower levels of architectures, i.e., at the chromatin and nucleosome levels. Upon gene activation and inactivation, folding and unfolding of the nucleosome structure and the chromatin fibers occur at limited loci of the genome. Namely, the structures of the chromosome are dynamic and mobile. Nevertheless, there are basic structural units that remain stable and constitute the fundamental chromosome architecture. 

The effect of the superhelical strain of the DNA template on the nucleosome structure can be investigated from the in vitro chromatin reconstitution system (for the detail of in vitro chromatin reconstitution, see sections 2.1 and 2.3). Interestingly, the efficiency of the reconstitution becomes higher as the lengths of the DNA used are longer (Hizume et al, 2004) (Fig. 3a-c). In the 3 kb reconstituted chromatin, one nucleosome could be formed in every 826 bp DNA on average, while in the 106 kb chromatin fibers, one nucleosome can be formed in every 260 bp of DNA. The chromatin reconstituted on the any length of linearized plasmid, the efficiency of the reconstitution becomes one nucleosome per 800 bp DNA. The treatment of the... 

McGhee JD, Felsenfeld G (1980) Nucleosome structure. Annu Rev Biochem 49 1115-1156 Melby TE, Ciampagho CN, Briscoe G, Erickson HP (1998) The symmetrical structure of structural maintenance of chromosomes (SMC) and MukB proteins long, antiparallel coiled coils, folded at a flexible hinge. J Cell Biol 142 1595-1604... 

Thibeault L, Hengartner M, Lagueux J, Poirier G, Muller S (1992) Rearrangements of the nucleosome structure in chromatin by poly (ADP-ribose). Biochim Biophys Acta 1121 317-324 Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410 227—230... 

There have been two basic approaches. First one involves isolation of the chromatin and nucleosome from the healthy and diseased cell line. The second approach is the reconstitution of the model target such as nucleosome followed by the association with the drug(s). The second approach has been extensively employed to identify the binding site in the protein-nucleic acid complex. A pre-knowledge about the components and their arrangements in the reconstituted system sometime makes it the preferred approach. Different biophysical, biochemical and genetic techniques have been employed to understand the mode of association and the effect of the drugs upon chromatin/nucleosome structure and function. 

Workman JL and Kingston RE (1998) Alteration of nucleosome structure as a mechanism of transcriptional regulation. Annu Rev Biochem 67 545-579... 

B. Audit, C. Thermes, C. Vaillant, Y. d Aubenton-Carafa, J.-F. Muzy, and A. Ameodo, Long-range correlations in genomic DNA A signature of the nucleosomal structure. Phys. Rev. Lett. 86, 2471-2474 (2001). 

An alternative approach to higher resolution nucleosome structure was to solve the complete NCP structure by increasing the diffracting resolution of... 

DNA sequence-dependent nucleosome structural and dynamic polymorphism. A role for H2B N-terminal tail proximal domain... 

A puzzling observation in the above mentioned investigation of the effect of positive supercoiling on nucleosome structure [51] was that the number of nucleosomes... 

Prunell, A. (1998) A topological approach to nucleosome structure and dynamics. The linking number paradox and other issues. Biophys. J. 74, 2531-2544. 

Sivolob, A., Lavelle, C., and Prunell, A. (2003) Sequence-dependent nucleosome structural and dynamic polymorphism. Potential involvement of histone H2B N-terminal tail proximal domain. J. Mol. Biol. 326, 49-63. 

Moreira, J.M. and Holmberg, S. (1998) Nucleosome structure of the yeast CHAl promoter analysis of activation-dependent chromatin remodeling of an RNA-polymerase-II-transcribed gene in TBP and RNA pol II mutants defective in vivo in response to acidic activators. EMBO J. 17, 6028-6038. 

---