Chromatin histones

Georges SA, Kraus WL, Luger K, Nyborg JK, Laybourn PJ (2002) p300-mediated tax transactivation from recombinant chromatin histone tail deletion mimics coactivator function. Mol Cell Biol 22 127-137... 

Boffa, L.C., Walker, J., Chen, T.A., Sterner, R., Mariani, M.R., and Allfrey, V.G. (1990) Factors effecting nucleosome structure in transcriptionally active chromatin. Histone acetylation, nascent RNA and inhibitors of RNA synthesis. Eur. J. Biochem. 194, 811-823. 

The state of our understanding of the physics of chromatin folding is such that the current knowledge about the structure and interaction of the basic components of chromatin— histones and DNA—enables us to develop the first quantitative models of the structure and dynamics of the chromatin fiber. Even so, these models are still at a very rudimentary stage data on the interaction of the histone tails... 

Calf (thymus chromatin) Histone redistribution No data + Polacow et al. 1976... 

This model is supported by other recent studies showing that poly(ADP-ribose) chains added in an in vitro system increase the accessibility of chromatin histones to histone-specific antibodies (Thiebault et al., 1992). 

In chromatin, a stretch of"linker" DNA (080 base pairs, typically 30 base pairs) is found between adjacent chromatosomes. The complete repeating structure is called a nucleosome which contains 8 core histones + histone HI + 168 base pairs of histone-bound DNA + linker DNA. In the electron microscope, nucleosomes can be "seen" as particles arranged along the thin DNA molecule and the structure is named, after its appearance, "beads on a string." In some regions of chromatin, histone HI may be absent, leaving nucleosome core particles connected by linker DNA. 

Jenuwein, T., and C. D. Allis. Translating the Histone Gode. Science 293, 1074—1079 (2001). [An in-depth article about chromatin, histones, and methylation.]... 

Biochemical and Morphological Study of the Poly( ADP-Ribosyl)ation of Native Chromatin, Histone HI Depleted Chromatin, and Core Particles... 

Fig. 90. Effect of chromatin histone from pea shoots on DNA -dependent RNA synthesis 50 pg DNA to 0,5 ml of standard reaction mixture containing enzyme (1.04 mg) + histone, as shovm on the graph (Huang and Bonner, 1962).

Another investigation (Marushide and Bonner, 1966) showed that chromatin isolated from the liver possessed about one-fifth of the activity of deproteinized DNA in relation to RNA-polymerase RNA synthesis. The factor responsible for this decreased activity was the chromatin histones. RNA synthesized on purified DNA consisted of complementary polynucleotides and was similar in its nucleotide composition to the DNA. RNA synthesized by chromatin consisted of noncomplementary molecules differing from total DNA in their nucleotide composition. On this basis, these workers claim that histones inhibit (close) specific zones in liver chromatin. 

Nucleus The nucleus is separated from the cytosol by a double membrane, the nuclear envelope. The DNA is complexed with basic proteins (histones) to form chromatin fibers, the material from which chromosomes are made. A distinct RNA-rich region, the nucleolus, is the site of ribosome assembly. The nucleus is the repository of genetic information encoded in DNA and organized into chromosomes. During mitosis, the chromosomes are replicated and transmitted to the daughter cells. The genetic information of DNA is transcribed into RNA in the nucleus and passes into the cytosol where it is translated into protein by ribosomes. 

The DNA in a eukaryotic cell nucleus during the interphase between cell divisions exists as a nucleoprotein complex called chromatin. The proteins of chromatin fall into two classes histones and nonhistone chromosomal proteins. 

If chromatin is swelled suddenly in water and prepared for viewing in the electron microscope, the nucleosomes are evident as beads on a string, dsDNA being the string (Figure 12.28). The structure of the histone octamer core has been determined by X-ray crystallography without DNA by E. N. Moudrianakis s laboratory (Figure 12.29) and wrapped with DNA by T. J. 

Chromatin is a noncovalent complex consisting of DNA and dedicated packing proteins, the histones. The name chromatin is derived from the Greek word chroma... 

Chromatin is composed of nucleosomes, where each comprise 147 base pairs of DNA wrapped around an octamer oftwo copies of each histone H2A, H2B, H3, and H4. Nucleosomes are folded into higher-order structures that are stabilized by linker histones. Chromatin structure can be altered by enzymes that posttranslationally modify histones (e.g., through phosphorylation, acetylation, methylation, or ubiquitination) or by ATP-driven chromatin-remodeling complexes that alter nucleosome position and/or composition. 

The antagonist-induced conformation of nuclear hormone receptors attracts co-repressors like Nco/SMRT (nuclear hormone receptor co-repressor/silencing mediator of retinoid and thyroid receptors) which further recruit other nuclear proteins with histone deacetylase activity. Their action leads to chromatin condensation, thus preventing the general transcription apparatus from binding to promoter regions. 

Due to the large amount of DNA present within the nucleus it must be carefully packaged. In the resting cell DNA is tightly compacted around basic histone proteins, excluding the binding of the enzyme RNA polymerase II, which activates the formation of mRNA. This conformation of the chromatin structure... 

Repression of genes is associated with reversal of this process under the control of histone deacetylases (HDACs). Deacetylation of histones increases the winding of DNA round histone residues, resulting in a dense chromatin structure and reduced access of transcription factors to their binding sites, thereby leading to repressed transcription of inflammatory genes. 

Histones are small, basic proteins required to condense DNA into chromatin. They have been first described and named in 1884 by Albrecht Kossel. There are five main histones HI, H2A, H2B, H3 andH4. An octamer of core histones H2A, H2B, H3 andH4 is located inside a nucleosome, the central building block of chromatin, with about 150 base pairs of DNA wrapped around. The basic nature of histones, mediated by the high content of lysine and arginine residues, allows a direct interaction with the acidic phosphate back bone of DNA. The fifth histone HI is located outside at the junction between nucleosomes and is referred to as the linker histone. Besides the main histones, so-called histone variants are known, which replace core histones in certain locations like centromers. 

An enzyme activity ascribed to many coactivators, which transfers acetyl groups to lysine residues of histone tails of the nucleosomes and thereby facilitate their disruption and the opening of the chromatin. 

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. 

A model called histone code theory includes more aspects of chromatin regulation which have been identified. The histone code theory predicts that histone acetylation and other posttranslational histone modifications serve as binding sites for regulatory proteins which mediate processes like gene transcription upon recruitment (see Fig. 2b) [3]. In this context histone modifications can be understood as... 

The exact role of individual histone acetylations will have to be determined in the context of other modifications and the number of lysine residues effected. However, the general importance of histone acetylation as a regulator for chromatin activity is undisputed. This leads to the intriguing possibility to develop drugs that target histone acetylation for therapeutic purposes. The primary targets for drug development are the histone acetyl transferases (HATs) and the histone deacetylases (HDACs) which introduce and remove histone acetylations [2, 3]. 

Enzyme activity ascribed to corepressors, which is the removal of acetyl groups from lysine residues of histone tails. Thereby the assembly of nucleosomes is maintained, which leads to a dense, transcriptional inactive chromatin structure. 

Histone tails are the N-terminal regions of histones which reach outside the nucleosomes. They are not essential for the formation in of nucleosomes but are required for the formation of higher-order chromatin structures. The histone tails are also known to be heavily posttranslationally modified by acetylation, phosphorylation, methylation, etc. and are important for the regulation of gene activity. 

The nucleosome represents the first level of DNA condensation and is the basic building block of all chromatin structures. It was discovered in 1973 and consists of a central histone octamer with about 150 base pairs of DNA wrapped around. 

Coactivators enhancing the transcriptional activity of steroid hormone receptors activators include SRC-1 (steroid-receptor co-activator 1) or TEF2 (transcriptional intermediary factor 2), which are recruited by the DNA/ steroid hormone receptor complex. Their main role is to attract other transcriptional coactivators with histone acetyltransferase activity in order to decondense chromatin and allow for the binding of components of the general transcription apparatus. 

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