What is the relationship between histones and nucleosomes in eukaryotic dna

Histone - Wikipedia

what is the relationship between histones and nucleosomes in eukaryotic dna

A nucleosome is a basic unit of DNA packaging in eukaryotes, consisting of a segment of DNA . The nucleosome core particle is composed of DNA and histone proteins. repeating nucleosomes with intervening "linker" DNA form a nm-fiber, described as "beads on a string", and have a packing ratio of about five to ten. The process by which the genetic code of DNA is copied into a strand of RNA Describe the relationship between DNA, chromatin, histones, and nucleosomes. Describe the structure of DNA; Describe how eukaryotic and prokaryotic DNA is arranged in . Figure The difference between the ribose found in RNA and the around proteins known as histones to form structures called nucleosomes.

Telomeres also perform another function: We discuss this type of repair and the other features of telomeres in Chapter 5. In yeast cells, the three types of sequences required to propagate a chromosome are relatively short typically less than base pairs each and therefore use only a tiny fraction of the information-carrying capacity of a chromosome.

Unit1E Eukaryotic DNA Packaging Chromatin

Although telomere sequences are fairly simple and short in all eucaryotes, the DNA sequences that specify centromeres and replication origins in more complex organisms are much longer than their yeast counterparts. For example, experiments suggest that human centromeres may contain up tonucleotide pairs. It has been proposed that human centromeres may not even require a stretch of DNA with a defined nucleotide sequence; instead, they may simply create a large, regularly repeating protein - nucleic acid structure.

Nucleosome

We return to this issue at the end of the chapter when we discuss in more general terms the proteins that, along with DNA, make up chromosomes. Recall from earlier in this chapter that human chromosome 22 contains about 48 million nucleotide pairs. Stretched out end to end, its DNA would extend about 1. This remarkable feat of compression is performed by proteins that successively coil and fold the DNA into higher and higher levels of organization.

Although less condensed than mitotic chromosomes, the DNA of interphase chromosomes is still tightly packed, with an overall compaction ratio of approximately fold. In the next sections we discuss the specialized proteins that make the compression possible. In reading these sections it is important to keep in mind that chromosome structure is dynamic. Not only do chromosomes globally condense in accord with the cell cycle, but different regions of the interphase chromosomes condense and decondense as the cells gain access to specific DNA sequences for gene expressionDNA repairand replication.

The packaging of chromosomes must therefore be accomplished in a way that allows rapid localized, on-demand access to the DNA. The complex of both classes of protein with the nuclear DNA of eucaryotic cells is known as chromatin.

Nucleosomes | BioNinja

Histones are present in such enormous quantities in the cell about 60 million molecules of each type per human cell that their total mass in chromatin is about equal to that of the DNA. Histones are responsible for the first and most basic level of chromosome organization, the nucleosomewhich was discovered in When interphase nuclei are broken open very gently and their contents examined under the electron microscopemost of the chromatin is in the form of a fiber with a diameter of about 30 nm Figure A.

The beads on a string represent the first level of chromosomal DNA packing. Figure Nucleosomes as seen in the electron microscope. A Chromatin isolated directly from an interphase nucleus appears in the electron microscope as a thread 30 nm thick.

B This electron micrograph shows a length of chromatin that has been experimentally more The structural organization of nucleosomes was determined after first isolating them from unfolded chromatin by digestion with particular enzymes called nucleases that break down DNA by cutting between the nucleosomes. After digestion for a short period, the exposed DNA between the nucleosome core particles, the linker DNA, is degraded.

Each individual nucleosome core particle consists of a complex of eight histone proteins—two molecules each of histones H2A, H2B, H3, and H4—and double-stranded DNA that is nucleotide pairs long. The histone octamer forms a protein core around which the double-stranded DNA is wound Figure Figure Structural organization of the nucleosome. A nucleosome contains a protein core made of eight histone molecules. As indicated, the nucleosome core particle is released from chromatin by digestion of the linker DNA with a nuclease, an enzyme that breaks more Each nucleosome core particle is separated from the next by a region of linker DNAwhich can vary in length from a few nucleotide pairs up to about The term nucleosome technically refers to a nucleosome core particle plus one of its adjacent DNA linkers, but it is often used synonymously with nucleosome core particle.

On average, therefore, nucleosomes repeat at intervals of about nucleotide pairs. For example, a diploid human cell with 6. The formation of nucleosomes converts a DNA molecule into a chromatin thread about one-third of its initial length, and this provides the first level of DNA packing. In assembling a nucleosome, the histone folds first bind to each other to form H3—H4 and H2A-H2B dimers, and the H3—H4 dimers combine to form tetramers.

Figure The structure of a nucleosome core particle, as determined by x-ray diffraction analyses of crystals.

Nucleosome - Wikipedia

Each histone is colored according to the scheme of Figurewith the DNA double helix in light gray. Reprinted by permission from K. Figure The overall structural organization of the core histones.

what is the relationship between histones and nucleosomes in eukaryotic dna

A Each of the core histones contains an N-terminal tail, which is subject to several forms of covalent modification, and a histone fold region, as indicated. B The structure of the histone more Figure The assembly of a histone octamer. An H3-H4 tetramer forms the scaffold of the octamer onto which two H2A-H2B dimers are added, to complete the assembly. The interface between DNA and histone is extensive: Nearly half of these bonds form between the amino acid backbone of the histones and the phosphodiester backbone of the DNA.

Numerous hydrophobic interactions and salt linkages also hold DNA and protein together in the nucleosome. For example, all the core histones are rich in lysine and arginine two amino acids with basic side chainsand their positive charges can effectively neutralize the negatively charged DNA backbone. These numerous interactions explain in part why DNA of virtually any sequence can be bound on a histone octamer core.

The path of the DNA around the histone core is not smooth; rather, several kinks are seen in the DNA, as expected from the nonuniform surface of the core. These histone tails are subject to several different types of covalent modifications, which control many aspects of chromatin structure.

We discuss these issues later in the chapter. As might be expected from their fundamental role in DNA packaging, the histones are among the most highly conserved eucaryotic proteins. For example, the amino acid sequence of histone H4 from a pea and a cow differ at only at 2 of the positions.

This strong evolutionary conservation suggests that the functions of histones involve nearly all of their amino acids, so that a change in any position is deleterious to the cell. This suggestion has been tested directly in yeast cells, in which it is possible to mutate a given histone gene in vitro and introduce it into the yeast genome in place of the normal gene.

As might be expected, most changes in histone sequences are lethal; the few that are not lethal cause changes in the normal pattern of gene expressionas well as other abnormalities. Despite the high conservation of the core histones, many eucaryotic organisms also produce specialized variant core histones that differ in amino acid sequence from the main ones.

For example, the sea urchin has five histone H2A variants, each of which is expressed at a different time during development. It is thought that nucleosomes that have incorporated these variant histones differ in stability from regular nucleosomes, and they may be particularly well suited for the high rates of DNA transcription and DNA replication that occur during these early stages of development.

Two main influences determine where nucleosomes form in the DNA. One is the difficulty of bending the DNA double helix into two tight turns around the outside of the histone octamer, a process that requires substantial compression of the minor groove of the DNA helix.

what is the relationship between histones and nucleosomes in eukaryotic dna

Because A-T-rich sequences in the minor groove are easier to compress than G -C-rich sequences, each histone octamer tends to position itself on the DNA so as to maximize A-T-rich minor grooves on the inside of the DNA coil Figure In addition, because the DNA in a nucleosome is kinked in several places, the ability of a given nucleotide sequence to accommodate this deformation can also influence the position of DNA on the nucleosome.

Figure The bending of DNA in a nucleosome. The DNA helix makes 1. This diagram is drawn approximately to scale, illustrating how the minor groove is compressed on the inside of the turn. Owing to certain structural features more These features of DNA probably explain some striking, but unusual, cases of very precise positioning of nucleosomes along a stretch of DNA.

For most of the DNA sequences found in chromosomes, however, there is no strongly preferred nucleosome - binding site ; a nucleosome can occupy any one of a number of positions relative to the DNA sequence. The second, and probably most important, influence on nucleosome positioning is the presence of other tightly bound proteins on the DNA.

Some bound proteins favor the formation of a nucleosome adjacent to them.

what is the relationship between histones and nucleosomes in eukaryotic dna

The human alpha-satellite palindromic DNA critical to achieving the nucleosome crystal structure was developed by the Bunick group at Oak Ridge National Laboratory in Tennessee. The structure of the nucleosome core particle is remarkably conserved, and even a change of over residues between frog and yeast histones results in electron density maps with an overall root mean square deviation of only 1.

Adjacent nucleosomes are joined by a stretch of free DNA termed "linker DNA" which varies from 10 - 80 bp in length depending on species and tissue type [19]. Digested chromatin is in the first lane; the second contains DNA standard to compare lengths.

Schema of nucleosome organization. The resulting image, via an electron microscope, is "beads on a string". The string is the DNA, while each bead in the nucleosome is a core particle.

The nucleosome core particle is composed of DNA and histone proteins. Because DNA portions of nucleosome core particles are less accessible for DNAse than linking sections, DNA gets digested into fragments of lengths equal to multiplicity of distance between nucleosomes, base pairs etc. Hence a very characteristic pattern similar to a ladder is visible during gel electrophoresis of that DNA. Due to the highly basic charge of all four core histones, the histone octamer is stable only in the presence of DNA or very high salt concentrations.

Histone - DNA interactions[ edit ] The nucleosome contains over direct protein-DNA interactions and several hundred water-mediated ones. Salt links and hydrogen bonding between both side-chain basic and hydroxyl groups and main-chain amides with the DNA backbone phosphates form the bulk of interactions with the DNA.

This is important, given that the ubiquitous distribution of nucleosomes along genomes requires it to be a non-sequence-specific DNA-binding factor. Although nucleosomes tend to prefer some DNA sequences over others, [31] they are capable of binding practically to any sequence, which is thought to be due to the flexibility in the formation of these water-mediated interactions.

In addition, non-polar interactions are made between protein side-chains and the deoxyribose groups, and an arginine side-chain intercalates into the DNA minor groove at all 14 sites where it faces the octamer surface.

The distribution and strength of DNA-binding sites about the octamer surface distorts the DNA within the nucleosome core. The DNA is non-uniformly bent and also contains twist defects. The twist of free B-form DNA in solution is However, the overall twist of nucleosomal DNA is only The N-terminal tail of histone H4, on the other hand, has a region of highly basic amino acidswhich, in the crystal structure, forms an interaction with the highly acidic surface region of a H2A-H2B dimer of another nucleosome, being potentially relevant for the higher-order structure of nucleosomes.

This interaction is thought to occur under physiological conditions also, and suggests that acetylation of the H4 tail distorts the higher-order structure of chromatin.

Higher order structure[ edit ] The current chromatin compaction model. The organization of the DNA that is achieved by the nucleosome cannot fully explain the packaging of DNA observed in the cell nucleus. Further compaction of chromatin into the cell nucleus is necessary, but is not yet well understood. The current understanding [26] is that repeating nucleosomes with intervening "linker" DNA form a nm-fiber, described as "beads on a string", and have a packing ratio of about five to ten.

Further compaction leads to transcriptionally inactive heterochromatin. Dynamics[ edit ] Although the nucleosome is a very stable protein-DNA complex, it is not static and has been shown to undergo a number of different structural re-arrangements including nucleosome sliding and DNA site exposure.

Depending on the context, nucleosomes can inhibit or facilitate transcription factor binding. Nucleosome positions are controlled by three major contributions: First, the intrinsic binding affinity of the histone octamer depends on the DNA sequence.

Second, the nucleosome can be displaced or recruited by the competitive or cooperative binding of other protein factors. Third, the nucleosome may be actively translocated by ATP-dependent remodeling complexes. Init was further revealed that CTCF binding sites act as nucleosome positioning anchors so that, when used to align various genomic signals, multiple flanking nucleosomes can be readily identified.