Chromatin structure

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. 

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. 

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. 

Figure 36-1. Electron micrograph of nucleosomes attached by strands of nucleic acid. (The bar represents 2.5 pm.) (Reproduced, with permission, from Oudet P, Gross-Bellard M, Chambon P Electron microscopic and biochemical evidence that chromatin structure is a repeating unit. Cell 1975 4 281.)...

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Porter, S., Larue, L., and Mintz, B. (1991). Mosaicism of tyrosinase-locus transcription and chromatin structure in dark vs. light melanocyte clones of homozygous chinchilla-mottled mice. Dev. Genet. 12 393-402. 

In the nuclei of all eukaryotic cells, DNA is tightly wrapped around an octamer of histone proteins and is compacted into a dense structure known as chromatin. In order to access the genetic information which is required in numerous essential cellular processes including DNA replication, gene expression and DNA repair, chromatin needs to be partially unwound. One important mechanism to regulate chromatin structure and thus to control the access of the genomic DNA is through histone modifications [1-6]. The histone octamer is composed of two copies of H2A, H2B, H3 and H4 core histone proteins. Their tails, that protrude out of the surface of the... 

Foster WG, McMahon A, Rice DC. 1996. Sperm chromatin structure is altered in cynomolgus monkeys with environmentally relevant blood lead levels. Toxicol Ind Health 12(5) 723-735. 

Much of the confusion was caused by the inadequacy of the staining procedures. By means of the HCl-Giemsa staining technique of Piekarski, many observations have been reported demonstrating the presence of chromatinic structures in bacteria. 

Hie chromatinic structures in E. coli from old cultures were too small to be resolved accurately. After transfer to fresh medium the chromatinic structures increased in size and gave rise to short, often dumbbell-shaped rods or chromosomes, which multiplied by splitting lengthwise in a plane more or less parallel to the short axis of the cell. A single cell of E. coli contained one chromatinic body or one or two pairs of these representing primary and secondary division products. 

The dynamic and differential methylation of lysine residues in histone tails plays a central role in the creation of the histone code and the regulation of chromatin structure and function that the code implies [12]. For example, different lysine methylation marks (KMe) are... 

Solomon MJ, Varshavsky A. Formaldehyde-mediated DNA-protein crosslinking a probe for in vivo chromatin structures. Proc. Natl. Acad. Sci. USA 1985 82 6470-6474. 

Orlando, V., Strutt, H., and Paro, R. (1997) Analysis of chromatin structure by in vivo formaldehyde cross-linking. Methods 11, 205-214. 

Co regulators of transcription — histone acetylases modulate chromatin structure 461... 

Lett, J.T. 1990. Damage to DNA and chromatin structure from ionizing radiations, and the radiation sensitivities of mammalian cells. Prog. Nucleic Acid Res. Molec. Biol. 39 305-352. 

One of the most-studied covalent modifications is the acetylation of the lysine residues of histone tails. The acetylation state of lysines of nucleosomal histones modulates chromatin structure and regulates gene transcriptional activity. The balance of lysine acetylation is controlled by the antagonistic action of two enzyme families histone deacetylases (HDACs) and histone acetyltransferases (HATs). In humans there are essentially three main HDAC subclasses [6]. 

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