Chromatin active genes

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. 

Munakata T, Adachi N, Yokoyama N, Kuzuhara T, Horikoshi M (2000) A human homolog of yeast anti-silencing factor has histone chaperone activity. Genes to Cells 5 221-233 Okuwaki M, Matsumoto K, Tsujimoto M, Nagata K (2001) Function of nucleophosmin/B23, a nuclear acidic protein, as a histone chaperone. FEBS Lett 506 272-276 Owen-Hughes T (2003) Colworth memorial lecture. Pathways for remodeling chromatin. Biochem. Soc.Trans 31 893-905... 

Figure 21.19 Development of a secondary carcinoma from a normal epithelium by effects of activated genes, i.e. oncogenes, and inactive tumour suppressor genes. It is somatic mutations in four or five genes in a given cell plus hypomethylation changes in histones and chromatin stracture that are involved. It is the accumulation of these genetic alterations, not the sequence, that determines the progression to a tumour cell.

Fig. 7. The model proposed by Szyf to explain the unmethylated status of active genes (for references and further details see Section 5.1). a) Inhibition of acetylation of the tails of core histones prevents active demethyiation. (b) When histone tails are acetylated, as in transcriptionally active chromatin regions, the demethyiase binding to the regions is enhanced, and the DNA is actively demethylated.

Hirschhorn, J.N., Brown, S.A., Clark, C.D., and Winston, F. (1992) Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. Genes Dev. 6, 2288-2298. 

Because these nucleases preferentially solubilize the DNA of active genes, methods have been developed to examine the proteins associated with the DNA. These methods take advantage of two main characteristics of the chromatin from active genes, its solubility in 100 mM NaCl and its solubility in moderate concentrations of Mg " " (2-5 mM). What has been found is that all four of the core histones H2A, H2B, H3, and H4 are present in these solubilized fractions [36-38]. Histone HI is... 

For a hormone to have a specific effect on gene activity, any increase in enzyme activity must result from de novo synthesis by newly formed mRNA. This increase in enzyme activity may or may not precede any general increase in metabolic activity. From the foregoing discussion on chromatin activity, it is clear that plant hormones largely either increase the activity of polymerase I or increase the synthesis of total RNA s. Claims that the hormones "activate" chromatin-bound polymerases and "modulate" the number of active sites on the chromatin (21) have not been substantiated. There are only two known examples of hormone-induced synthesis of specific mRNA s. The classic example is the barley aleurone cells, in which GA treatment induces de novo synthesis and release of K-amylase (58, 59, 60), protease (61), and possibly as many as ten proteins (62). 

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