Histone protein octamer

In 1991, Luger et al. revealed by X-ray analysis the crystal structure of a natural DNA-histone complex. The X-ray structure shows in atomic detail how the histone protein octamer is assembled and how the base pairs of DNA are organized into a superhelix around it [74]. Since then this protein structure with cationic amino acids on the surface has acted as a model for the rational design of dendritic polymer-based gene vectors to mimic the globular shape of the natural histone complex [75-77]. 

In the nucleosome, the DNA is supercoiled in a left-handed helix over the surface of the disk-shaped histone octamer (Figure 36-2). The majority of core histone proteins interact with the DNA on the inside of the supercoil without protruding, though the amino terminal tails of all the histones probably protrude outside of this structure and are available for regulatory covalent modifications (see Table 36-1). 

Much of the DNA is associated with histone proteins to form a structure called the nucleosome. Nucleo-somes are composed of an octamer of histones and 150 bp of DNA. 

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... 

DNA is packaged in the nucleus into the form of chromatin. Chromatin is a nucleoprotein complex composed of histone and non-histone proteins, DNA and RNA and it exhibits a repeating structure (van Holde, 1988). The basal unit of chromatin, the nucleosome, is composed of a histone octamer (two each of H2A, H2B, H3 and H4) around which two superhelical turns of DNA are wrapped (van Holde, 1988). The structure of both the histone octamer (Arents et al, 1991)... 

Regulation of transcription is a central mechanism by which cells respond to developmental and environmental cues. RNA polymerase Il-mediated transcription in eukaryotes is to a large extent regulated at the level of chromatin, which forms a physical barrier for the binding of proteins to the promoter region of a target gene. The basic unit of chromatin is the nucleosome, which consists of an octamer of histone proteins around which the DNA is wrapped (see Fig. la). 

The family of HDAC enzymes has been named after their first substrate identified, i.e., the nuclear histone proteins. Histone proteins (H2A, H2B, H3 and H4) form an octamer complex, around which the DNA helix is wrapped in order to establish a condensed chromatin structure. The acetylation status of histones is in a dynamic equilibrium governed by histone acetyl transferases (HATs), which acetylate and HDACs which are responsible for the deacetylation of histone tails (Fig. 1). Inhibition of the HDAC enzyme promotes the acetylation of nucleosome histone tails, favoring a more transcriptionally competent chromatin structure, which in turn leads to altered expression of genes involved in cellular processes such as cell prohferation, apoptosis and differentiation. Inhibition of HDAC activity results in the activation of only a limited set of pre-programmed genes microarray experiments have shown that 2% of all genes are activated by structmally different HDAC inhibitors [1-5]. In recent years, a growing number of additional nonhistone HDAC substrates have been identified, which will be discussed in more detail below. 

The histones present in chromatin are of five major types HI, H2a, H2b, H3, and H4 (table 25.2). The lysine-rich histone HI is not present in the nucleosome core particles, as evidenced by its release on extensive nuclease treatment and the finding that HI is the only histone that readily exchanges between free and DNA-bound histone. HI may play a key role in the conversion of chromatin to the highly compacted chromosome that occurs immediately before cell division. The other eight histones, two each of the other four histones, form the protein core of the nucleosome. These protein octamers do not come apart even when chromosomes duplicate. 

Nucleosome. A complex of DNA and an octamer of histone proteins in which a small stretch of the duplex is wrapped around a molecular bead of histone. 

The amino terminal tails of the four core histones contain lysines that are acetylated by HATs and deacetylated by HDACs. The histone octamer (H2A, H2B, H3, H4)2 is represented as a cylinder wrapped by DNA. It is thought that neutralization of the positive charges on the histone tails results in alterations of the nucleosome structure and of associated non-histone proteins that may lead to a... 

In eukaryotic cells, DNA is associated with about an equal mass of histone proteins in a highly condensed nu-cleoproteln complex called chromatin. The building block of chromatin is the nucleosome, consisting of a histone octamer around which is wrapped 147 bp of DNA (see Figure 10-21). 

The nucleosome consists of a 200-base-pair (bp) DNA strand making two left-handed coils around an octamer of histone proteins consisting of two copies each of histones H2A, H2B, H3, and H4, and a single copy of the histone HI (Fig. 6.3). 

Fig. 6.3. A DNA thread making two left-handed coils around each of a series of protein spools. A single spool consists of an octamer of histone proteins, two each of H2A, H2B, H3, and H4. The ninth histone protein, H1, may be located in the linker region between spools immediately adjacent to the spool. The DNA and histones make up the nucleosome. (From Calladine CR, Drew HR. Understanding DNA The Molecule and How It Works, 2nd Ed. New York Academic Press, 1997 with permission.)...

In eukaryotic cells, DNA is packaged into a highly compacted and condensed nucleoprotein structure called chromatin. Biochemical studies and electron microscopy indicated that DNA in eukaryotic chromatin is folded as regular units, each of which contains 146 base pairs of DNA and a core of histone proteins. Structurally, DNA makes approximately 1.8 turns around a central histone octamer that consists of two molecules of each of the four core histones H2A, H2B, H3, and H4. The combination of a histone core and associated DNA makes up the nucleosome. Nucleo-somes are linked by 20-100 base pairs (bp) of linker DNA, so as to form a beadlike nucleosomal array. In conjunction with the linker histone, Hl,... 

Nucleosome The first-order structural unit for the packing of DNA in chromatin, consisting of 146 bp of DNA wrapped 1.75 times around a core octamer of histone proteins. Successive nucleosomes are connected by stretches of linker DNA. 

Figure 5.2 Views from an X-ray crystal structure of a nucleosome (PDB ID 1KX3), consisting of 146 bp of DNA (orange/dark blue) wrapped around the histone octamer, which is made up of pairs of histone proteins H2A (pink), H2B (yellow), H3 (green) and H4 (blue).

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