Chromatin variation

Chromatin remodeling, transcription factor modification by various enzyme activities, and the communication between the nuclear receptors and the basal transcription apparatus are accomplished by protein-protein interactions with one or more of a class of coregulator molecules. The number of these coregulator molecules now exceeds 100, not counting species variations and splice variants. The first of these to be described was the CREB-binding protein, CBP. CBP, through an amino terminal domain, binds to phosphorylated serine 137 of CREB and mediates transactivation in response to cAMP. It thus is described as a coactivator. CBP and... 

Also, local changes in the structural and chemical variation of DNA may have important effects on the overall extent of chromatin folding. For instance, transitions from the B to the Z form of DNA will result in nucleosome dissolution (as discussed earlier) and this could affect the folding of the fiber. As well, chemical modifications of the bases such as methylation have been shown to increase the folding of the chromatin fiber when linker histones are present [250] although the mechanism involved in this later case remains to be elucidated. 

Histone variation and chromatin stability. A few selected examples... 

Jeppesen, P., Mitchell, A., Turner, B.M., and Perry, P. (1991) Antibodies to defined histone epitopes reveal variations in chromatin conformation and underacetylation of centric heterochromatin in human metaphase chromosomes. Chromosoma 100, 322-332. 

Thus, to reflect correctly the state of the system at a certain temperature, one needs a simulation technique that generates an ensemble of chain conformations whose statistical properties reflect those of the real chain at thermodynamic equilibrium. The chromatin fiber models that are discussed in the following use one or the other variation of such techniques. 

The DNA molecules in eukaryotic cells are considerably larger than those in bacteria and are organized into complex nucleoprotein structures (chromatin p. 938). The essential features of DNA replication are the same in eukaryotes and prokaryotes, and many of the protein complexes are functionally and structurally conserved. However, some interesting variations on the general principles discussed above promise new insights into the regulation of replication and its link with the cell cycle. 

Wardman P, Dennis MF, Everett SA, Patel KB, Stratford MRL, Tracy M (2003) Radicals from one-electron reduction of nitro compounds, aromatic N-oxides and quinones the kinetic basis for hypoxia-selective, bioreductive drugs. Biochem Soc Symp 61 171-194 Warman JM, de Haas MP, Hummel A, van Lith D, VerberneJB, Loman H (1980) A pulse radiolysis conductivity study of frozen aqueous solutions of DNA. Int J Radiat Biol 38 459-459 Warman JM, de Haas MP, Rupprecht A (1996) DNA a molecular wire Chem Phys Lett 249 319-322 Warters RL, Lyons BW (1992) Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. Radiat Res 130 309-318 Warters RL, Hofer KG, Harris CR, Smith JM (1977) Radionuclide toxicity in cultured mammalian cells Elucidation of the primary site of radiation damage. Curr Top Radiat Res Q 12 389-407 Weiland B, Huttermann J (1998) Free radicals from X-irradiated, dry and hydrated lyophilized DNA as studies by electron spin resonance spectroscopy analysis of spectral components between 77 K and room temperature. Int J Radiat Biol 74 341-358 Weinfeld M, Soderlind K-JM (1991) 32P-Postlabeling detection of radiation-induced DNA-damage identification and estimation of thymine glycols and phosphoglycolate termini. Biochemistry 30 1091-1097... 

Variations in the chromatin pattern of the cells may be explained by DNA repair processes (El-Khattabi et al, 1997 Murata et al., 1998 Harley, 2001). While these data may be relevant to higher radiation doses required for therapy where present tolerable doses are merely palliative, protraction does lengthen the time and therefore the cost required to dehver that dose. 

A theoretical analysis of the scattering by an array of fibres indicates that the intensity and position of the interference band are determined by the parameter y, which is the ratio of the centre-to-centre distance between fibres to the fibre diameter. The variation in the position of the interference band from different types of nuclei under similar ionic conditions can thus be attributed to differences in the chromatin fibre diameter... 

Fig. 28. The three basic scattering functions from the shape Iy(Q), the cross-term /vf(0 nd the fluctuations /p(2) fro contrast variation studies on the chromatin core particle [387]. I (Q) corresponds to the scattering from the shape as observed at infinite contrast where there is no influence from the internal structure Pp(r) from the DNA and protein components. Its Guinier region gives the Rq of the Stuhrmann plot. /p(2) is the internal structure function and should correspond to the scattering curve measured at the matchpoint of the core particle in 48% H20. The cross-term /vp(2) is the correlation of the shape and internal structures. The calculated curves from 3 models are shown in...

Thin-sectioning for EM observation is a standard technique that provides important information about meiotic cells, especially when three-dimensional (3D) reconstructions are performed (Wettstein and Sotelo, 1967 Solari, 1970 Holm and Rasmussen, 1977). The use of this technique is especially suitable for establishing topographical relationships among nuclear structures and for observation of variations in chromatin packing. A wide variety of fixatives, embedding, and staining procedures may be used for this purpose and are available in the literature (Hayat, 1989). Methods have been previously described (Solari, 1970). 

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