All rights reserved. Figure Detail. Figure 2: Electron micrograph of chromatin: the beads on a string In this micrograph, nucleosomes are indicated by arrows. Chromatin history: our view from the bridge. Nature Reviews Molecular Cell Biology 4, The basic repeating structural and functional unit of chromatin is the nucleosome, which contains eight histone proteins and about base pairs of DNA Van Holde, ; Wolffe, The observation by electron microscopists that chromatin appeared similar to beads on a string provided an early clue that nucleosomes exist Olins and Olins, ; Woodcock et al.
Another clue came from chemically cross-linking i. This experiment demonstrated that H2A, H2B, H3, and H4 form a discrete protein octamer, which is fully consistent with the presence of a repeating histone-containing unit in the chromatin fiber.
Today, researchers know that nucleosomes are structured as follows: Two each of the histones H2A, H2B, H3, and H4 come together to form a histone octamer, which binds and wraps approximately 1. The addition of one H1 protein wraps another 20 base pairs, resulting in two full turns around the octamer, and forming a structure called a chromatosome Box 4 in Figure 1.
The resulting base pairs is not very long, considering that each chromosome contains over million base pairs of DNA on average. Therefore, every chromosome contains hundreds of thousands of nucleosomes, and these nucleosomes are joined by the DNA that runs between them an average of about 20 base pairs.
One such enzyme, micrococcal nuclease MNase , has the important property of preferentially cutting the linker DNA between nucleosomes well before it cuts the DNA that is wrapped around octamers. By regulating the amount of cutting that occurs after application of MNase, it is possible to stop the reaction before every linker DNA has been cleaved.
At this point, the treated chromatin will consist of mononucleosomes, dinucleosomes connected by linker DNA , trinucleosomes, and so forth Hewish and Burgoyne, If DNA from MNase-treated chromatin is then separated on a gel, a number of bands will appear, each having a length that is a multiple of mononucleosomal DNA Noll, The simplest explanation for this observation is that chromatin possesses a fundamental repeating structure.
When this was considered together with data from electron microscopy and chemical cross-linking of histones, the "subunit theory" of chromatin Kornberg, ; Van Holde et al. The subunits were later named nucleosomes Oudet et al. The model of the nucleosome that crystallographers constructed from their data is shown in Figure 3.
Note that only eukaryotes i. Prokaryotes, such as bacteria , do not. Figure 4: Electron micrograph of chromatin A 30nm fiber of chromatin. The packaging of DNA into nucleosomes shortens the fiber length about sevenfold.
In other words, a piece of DNA that is 1 meter long will become a "string-of-beads" chromatin fiber just 14 centimeters about 6 inches long.
Despite this shortening, a half-foot of chromatin is still much too long to fit into the nucleus, which is typically only 10 to 20 microns in diameter. Therefore, chromatin is further coiled into an even shorter, thicker fiber, termed the "nanometer fiber," because it is approximately 30 nanometers in diameter Figure 4. Over the years, there has been a great deal of speculation concerning the manner in which nucleosomes are folded into nanometer fibers Woodcock, Part of the problem lies in the fact that electron microscopy is perhaps the best way to visualize packaging, but individual nucleosomes are hard to discern after the fiber has formed.
In addition, it also makes a difference whether observations are made using isolated chromatin fibers or chromatin within whole nuclei. Thus, the nanometer fiber may be highly irregular and not quite the uniform structure depicted in instructive drawings such as Figure 1 Bednar et al. Interestingly, histone H1 is very important in stabilizing chromatin higher-order structures, and nanometer fibers form most readily when H1 is present.
Processes such as transcription and replication require the two strands of DNA to come apart temporarily, thus allowing polymerases access to the DNA template. However, the presence of nucleosomes and the folding of chromatin into nanometer fibers pose barriers to the enzymes that unwind and copy DNA. Generally speaking, there are two major mechanisms by which chromatin is made more accessible:. When eukaryotic cells divide, genomic DNA must be equally partitioned into both daughter cells.
To accomplish this, the DNA becomes highly compacted into the classic metaphase chromosomes that can be seen with a light microscope. Once a cell has divided, its chromosomes uncoil again. Comparing the length of metaphase chromosomes to that of naked DNA, the packing ratio of DNA in metaphase chromosomes is approximately 10, depending on the chromosome.
This can be thought of as akin to taking a rope as long as a football field and compacting it down to less than half an inch.
This level of compaction is achieved by repeatedly folding chromatin fibers into a hierarchy of multiple loops and coils Figure 1. Exactly how this is accomplished is unclear, but the phosphorylation of histone H1 may play a role. Indeed, this is just one area of DNA packaging that researchers will continue to explore in the years to come.
Bednar, J. Nucleosomes, linker DNA, and linker histones form a unique structural motif that directs the higher-order folding and compaction of chromatin.
Proceedings of the National Academy of Sciences 95 , — Fischle, W. Histone and chromatin cross-talk. Current Opinion in Cellular Biology 15 , — Hewish, D. Chromatin sub-structure. The digestion of chromatin DNA at regularly spaced sites by a nuclear deoxyribonuclease.
Biochem Biophys Res Commun 52 , Kornberg, R. Chromatin structure: A repeating unit of histones and DNA. Science , — Luger, K. Crystal structure of the nucleosome core particle at 2. Nature , — link to article. Noll, M. Subunit structure of chromatin. Olins, A. Spheroid chromatin units v bodies. Olins, D. Chromatin history: Our view from the bridge.
For example, the looping of nucleosome-containing fibers brings specific regions of chromatin together, thereby influencing gene expression. In fact, the organized packing of DNA is malleable and appears to be highly regulated in cells.
Chromatin packing also offers an additional mechanism for controlling gene expression. Specifically, cells can control access to their DNA by modifying the structure of their chromatin. Highly compacted chromatin simply isn't accessible to the enzymes involved in DNA transcription , replication , or repair. Thus, regions of chromatin where active transcription is taking place called euchromatin are less condensed than regions where transcription is inactive or is being actively inhibited or repressed called heterochromatin Figure 6.
Figure 6: The structure of chromatin in interphase Heterochromatin is more condensed than euchromatin. Typically, the more condensed chromatin is, the less accessible it is by transcription factors and polymerases. The dynamic nature of chromatin is regulated by enzymes. For example, chromatin can be loosened by changing the position of the DNA strands within a nucleosome. This loosening occurs because of chromatin remodeling enzymes, which function to slide nucleosomes along the DNA strand so that other enzymes can access the strand.
This process is closely regulated and allows specific genes to be accessed in response to metabolic signals within the cell. Another way cells control gene expression is by modifying their histones with small chemical groups, such as methyl and acetyl groups in the N-terminal tails that extend from the core particle. Different enzymes catalyze each kind of N-terminal modification.
Scientists occasionally refer to the complex pattern of histone modification in cells as a "histone code. In electron micrographs, eukaryotic interphase chromatin appears much like a plate of spaghetti — in other words, there is no obvious pattern of organization.
In recent years, however, investigators have begun using fluorescent probes for each of the different interphase chromosomes. In doing so, they have discovered that these chromosomes have functional and decidedly nonrandom arrangements. One of the first things these scientists noted was that uncondensed chromosomes occupy characteristic regions of the nucleus, which they termed chromosome territories.
The spatial localization of these territories is thought to be important for gene expression. In fact, with the advent of gene-specific probes, researchers are beginning to understand how the arrangement of chromosome territories can bring particular genes closer together. A second major observation related to chromosome territories is that the position of chromosomes relative to one another differs from cell to cell.
Such differences reflect variation in gene expression patterns. This page appears in the following eBook. Aa Aa Aa. What Are Chromosomes? How Are Eukaryotic Chromosomes Structured? Figure 3. Figure 6: The structure of chromatin in interphase. Heterochromatin is more condensed than euchromatin. How Are Chromosomes Organized in the Nucleus? The prokaryotic genome typically exists in the form of a circular chromosome located in the cytoplasm.
In eukaryotes, however, genetic material is housed in the nucleus and tightly packaged into linear chromosomes. Chromosomes are made up of a DNA-protein complex called chromatin that is organized into subunits called nucleosomes. The way in which eukaryotes compact and arrange their chromatin not only allows a large amount of DNA to fit in a small space, but it also helps regulate gene expression.
Cell Biology for Seminars, Unit 2. Topic rooms within Cell Biology Close. No topic rooms are there. Or Browse Visually. Student Voices. The post-translational modifications to histone proteins underlie the mechanisms of epigenetics, which are defined as alterations to gene expression without changes to the DNA sequence.
The ability for DNA packaging to be modified at various stages of the cell cycle is important in both DNA replication and cell division as well as transcription. Replication occurs at many origins of replication throughout the DNA strand to accelerate the replication of the entire genome, with each origin separated by approximately , base pairs.
The DNA does not interact with histones during this process to allow for the propagation of the polymerase enzymes. However, when the process is complete, the DNA must reintegrate with the histones to reform nucleosomes and eventually the supercoiled chromosome structure during mitosis. Following cell division, the DNA must again separate from the histone proteins to undergo transcription.
This capability for the DNA-histone interactions to be modulated is crucial for the proper growth and function of a cell with malfunctions contributing to disease like hypermethylation in cancer.
0コメント