Chromatin is the complex of DNA and protein that makes up chromosomes. A chromosome is an organized structure of DNA and Protein that is found in cells. It is found inside the nuclei of eukaryotic cells, and within the nucleoid in prokaryotic cells. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called In Prokaryotes, the nucleoid (meaning nucleus-like) is an irregularly-shaped region within the cell of Prokaryotes where the Genetic material ^[1] The major proteins involved in chromatin are histone proteins, although many other chromosomal proteins have prominent roles too. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl In Biology, histones are the chief Protein components of Chromatin. The functions of chromatin are to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis, and to serve as a mechanism to control expression. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei In Biology or life science meiosis (pronounced my-oh-sis is a process of reductional division in which the number of chromosomes per cell is cut in half Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such Changes in chromatin structure are affected mainly by methylation (DNA and proteins) and acetylation (proteins). Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. Acetylation (or in IUPAC nomenclature ethanoylation) describes a reaction that introduces an Acetyl Functional group into an Organic compound Chromatin structure is also relevant to DNA replication and DNA repair. DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome.

Chromatin is easily visualised by staining, hence its name, which literally means coloured material.

Fig. 1: The major structures in DNA compaction; DNA, the nucleosome, the 10nm "beads-on-a-string" fibre, the 30nm fibre and the metaphase chromosome. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Nucleosomes form the fundamental repeating units of eukaryotic Chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring Metaphase from the Ancient Greek μετά (after and φάσις (stage is a stage of Mitosis in the eukaryotic Cell cycle in which A chromosome is an organized structure of DNA and Protein that is found in cells.

Basic Structure

Simplistically, there are three levels of chromatin organization (Fig. 1):

1. DNA wrapping around nucleosomes - The "beads on a string" structure. Nucleosomes form the fundamental repeating units of eukaryotic Chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring
2. A 30 nm condensed chromatin fiber consisting of nucleosome arrays in their most compact form. A nanometre ( American spelling: nanometer, symbol nm) ( Greek: νάνος nanos dwarf; μετρώ metrό count) is a
3. Higher level DNA packaging into the metaphase chromosome. A chromosome is an organized structure of DNA and Protein that is found in cells. . . .

These structures do not occur in all eukaryotic cells. Examples of cells with more extreme packaging are spermatozoa andmjh avian red blood cells. A spermatozoon or spermatozoan ( pl spermatozoa) from the Ancient Greek σπέρμα (seed and ζῷον (living being and more commonly known Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood

During spermiogenesis, the spermatid's chromatin is remodelled into a more tightly packaged, compact, almost crystal-like structure. Spermiogenesis is the final stage of Spermatogenesis which sees the maturation of Spermatids into mature motile spermatozoa. The term spermatid refers to the Haploid male Gametid that results from division of secondary Spermatocytes As a result of Meiosis, each spermatid This process is associated with the cessation of transcription and involves nuclear protein exchange. Transcription is the synthesis of RNA under the direction of DNA In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed The histones are mostly displaced, and replaced by protamines (small, arginine-rich proteins). Protamines are small Arginine -rich nuclear Proteins that replace Histones late in the Haploid phase of Spermatogenesis Arginine (abbreviated as Arg or R) is an α- Amino acid. The L-form is one of the 20 most common natural amino acids

It should also be noted that during mitosis, while most of the chromatin is tightly compacted, there are small regions that are not as tightly compacted. These regions often correspond to promoter regions of genes that were active in that cell type prior to entry into mitosis. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei The lack of compaction of these regiongs is called bookmarking, which is an epigenetic mechanism believed to be important for transmitting to daughter cells the "memory" of which genes were active prior to entry into mitosis. In Genetics and Epigenetics, bookmarking is a biological phenomenon believed to function as an epigenetic mechanism for transmitting Cellular memory of In Biology, the term epigenetics refers to changes in Gene expression caused by mechanisms other than changes in the underlying DNA sequence This bookmarking mechanism is needed to help transmit this memory because transcription ceases during mitosis. In Genetics and Epigenetics, bookmarking is a biological phenomenon believed to function as an epigenetic mechanism for transmitting Cellular memory of Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei

Levels of organization

History

During interphase

The structure of chromatin during interphase is optimised to allow easy access of transcription and DNA repair factors to the DNA while compacting the DNA into the nucleus. Interphase is the phase of the Cell cycle in which the cell spends the majority of its time and performs the majority of its purposes including preparation for Cell Transcription is the synthesis of RNA under the direction of DNA DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome. In Cell biology, the nucleus (pl nuclei; from Latin la ''nucleus'' or la ''nuculeus'' "little nut" or kernel is a membrane-enclosed The structure varies depending on the access required to the DNA. Genes that require regular access by RNA polymerase require the looser structure provided by euchromatin. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA.

Change in structure

Chromatin undergoes various forms of change in its structure. Histone proteins, the foundation blocks of chromatin, are modified by various post-translational modification to alter DNA packing. In Biology, histones are the chief Protein components of Chromatin. Acetylation results in the loosening of chromatin and lends itself to replication and transcription. When methylated they hold DNA together strongly and restrict access to various enzymes. A recent study showed that there is a bivalent structure present in the chromatin: methylated lysine residues at location 4 and 27 on histone 3. It is thought that this may be involved in development; there is more methylation of lysine 27 in embryonic cells than in differentiated cells, whereas lysine 4 methylation positively regulates transcription by recruiting nucleosome remodeling enzymes and histone acetylases. ^[2]

Polycomb-group proteins play a role in regulating genes through modulation of chromatin structure. Polycomb-group proteins are a family of proteins first discovered in fruit flies that can remodel Chromatin such that Transcription factors cannot bind ^[3]

For additional information see Histone modifications in chromatin regulation and RNA polymerase control by chromatin structure

DNA structure

The structures of A-, B- and Z-DNA. In Biology, histones are the chief Protein components of Chromatin. RNA polymerase II (also called RNAP II and Pol II) is an enzyme found in eukaryotic cells

Main articles: Mechanical properties of DNA and Z-DNA

The vast majority of DNA within the cell is the normal DNA structure. The mechanical properties of DNA, which are directly related to its structure are a significant problem for cells. Z-DNA is one of the many possible double helical structures of DNA. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known However in nature DNA can form three structures, A-, B- and Z-DNA. Z-DNA is one of the many possible double helical structures of DNA. A and B chromosomes are very similar, forming right-handed helices, while Z-DNA is a more unusual left-handed helix with a zig-zag phosphate backbone. Z-DNA is thought to play a specific role in chromatin structure and transcription because of the properties of the junction between B- and Z-DNA. Transcription is the synthesis of RNA under the direction of DNA

At the junction of B- and Z-DNA one pair of bases is flipped out from normal bonding. These play a dual role of a site of recognition by many proteins and as a sink for torsional stress from RNA polymerase or nucleosome binding. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA.

The nucleosome and "beads-on-a-string"

Main articles: Nucleosome, Chromatosome and Histone

A cartoon representation of the nucleosome structure. Nucleosomes form the fundamental repeating units of eukaryotic Chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring A chromatosome is essentially a Nucleosome with one bound linker histone e In Biology, histones are the chief Protein components of Chromatin. From PDB 1KX5. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography

The basic repeat element of chromatin is the nucleosome, interconnected by sections of linker DNA, a far shorter arrangement than pure DNA in solution.

In addition to the core histones there is the linker histone, H1, which contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome, together with histone H1, is known as a chromatosome. Chromatosomes, connected by about 20 to 60 base pairs of linker DNA, form an approximately 10 nm "beads-on-a-string" fibre. (Fig. 1-2).

The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging. There is, however, some preference in the sequences the nucleosomes will bind. This is largely through the properties of DNA; adenosine and thymine are more favorably compressed into the inner minor grooves. Adenosine is a Nucleoside composed of a Molecule of Adenine attached to a Ribose sugar molecule ( Ribofuranose) moiety via a β-N9- Thymine is one of the four bases in the Nucleic acid of DNA that make up the letters ATGC This means nucleosomes bind preferentially at one position every 10 base pairs - where the DNA is rotated to maximise the number of A and T bases which will lie in the inner minor groove. (See mechanical properties of DNA. The mechanical properties of DNA, which are directly related to its structure are a significant problem for cells. )

30 nm chromatin fibre

Two proposed structures of the 30nm chromatin filament.
Left: 1 start helix "solenoid" structure.
Right: 2 start loose helix structure.
Note: the nucleosomes are omitted in this diagram - only the DNA is shown.

The "beads-on-a-string" structure in turn coils into a 30 nm diameter helical structure known as the 30nm fibre or filament. The precise structure of the chromatin fibre in the cell is not known in detail, and there is still some debate over this.

This level of chromatin structure is thought to be the form of euchromatin, which contains actively transcribed genes. Euchromatin is a lightly packed form of Chromatin that is rich in Gene concentration and is often (but not always under active transcription. EM studies have demonstrated the 30 nm fibre is highly dynamic such that it unfold into a 10 nm fiber ("beads-on-a-string") structure when transversed by an RNA polymerase engaged in transcription.

Four proposed structures of the 30nm chromatin filament for DNA repeat length per nucleosomes ranging from 177 to 207 bp.
Linker DNA in yellow and nucleosomal DNA in pink.

The existing models commonly accept that the nucleosomes lie perpendicular to the axis of the fibre, with linker histones arranged internally. A stable 30 nm fibre relies on the regular positioning of nucleosomes along DNA. Linker DNA is relatively resistant to bending and rotation. This makes the length of linker DNA critical to the stability of the fibre, requiring nucleosomes to be separated by lengths that permit rotation and folding into the required orientation without excessive stress to the DNA. In this view, different length of the linker DNA should produce different folding topologies of the chromatin fiber. Recent theoretical work, based on electron-microscopy images^[4] of reconstituted fibers support this view. ^[5]

Spatial organization of chromatin in the cell nucleus

The layout of the genome within the nucleus is not random - specific regions of the genome are always found in certain areas. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby Specific regions of the chromatin are thought to be bound to the nuclear membrane, while other regions are bound together by protein complexes. The nuclear envelope (NE(also known as the perinuclear envelope, nuclear membrane, nucleolemma or karyotheca) is a double lipid bilayer that The layout of this is not, however, well characterised apart from the compaction of one of the two X chromosomes in mammalian females into the Barr body. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands Female (♀ is the Sex of an Organism, or a part of an organism which produces ova (egg cells In those species (including humans in which sex is determined by the presence of the Y or X Chromosome rather than the diploidy of the X or Z a Barr body is This serves the role of permanently deactivating these genes, which prevents females getting a 'double dose' of relative to males. Dosage compensation is a genetic regulatory mechanism which operates to equalize the Phenotypic expression of characteristics determined by genes on the X chromosome Male (♂ refers to the sex of an organism or part of an organism which produces small mobile Gametes called spermatozoa.

Metaphase chromatin

Karyogram of human male using Giemsa staining, showing the classic metaphase chromatin structure. Giemsa stain, named after Gustav Giemsa, an early malariologist is used for the histopathological diagnosis of Malaria and other Parasites It is a mixture Metaphase from the Ancient Greek μετά (after and φάσις (stage is a stage of Mitosis in the eukaryotic Cell cycle in which

The metaphase structure of chromatin differs vastly to that of interphase. Metaphase from the Ancient Greek μετά (after and φάσις (stage is a stage of Mitosis in the eukaryotic Cell cycle in which It is optimised for physical strength and manageability, forming the classic chromosome structure seen in karyotypes. A chromosome is an organized structure of DNA and Protein that is found in cells. A karyotype is the characteristic Chromosome complement of a Eukaryote Species. The structure of the condensed chromosome is thought to be loops of 30nm fibre to a central scaffold of proteins. It is, however, not well characterised.

The physical strength of chromatin is vital for this stage of division to prevent shear damage to the DNA as the daughter chromosomes are separated. To maximise strength the composition of the chromatin changes as it approaches the centromere, primarily through alternative histone H1 anologues.

Non-histone chromosomal proteins

The proteins that are found associated with isolated chromatin fall into several functional categories:

• chromatin-bound enzymes
• high mobility group (HMG) proteins
• transcription factors
• scaffold proteins
• transition proteins (testis specific proteins)
• protamines (present in mature sperm)

Enzymes associated with chromatin are those involved in DNA transcription, replication and repair, and in post-translational modification of histones. In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Scaffold proteins bring together various other proteins in a Signaling pathway and allows for their interaction They include various types of nucleases and proteases. Scaffold proteins encompass chromatin proteins such as insulators, domain boundary factors and cellular memory modules (CMMs). Insulator may refer to Insulator (genetics Insulator (electrical Thermal insulation Building

Chromatin: alternative definitions

1. Simple and concise definition: Chromatin is DNA plus the proteins (and RNA) that package DNA within the cell nucleus.
2. A biochemists’ operational definition: Chromatin is the DNA/protein/RNA complex extracted from eukaryotic lysed interphase nuclei. Just which of the multitudinous substances present in a nucleus will constitute a part of the extracted material will depend in part on the technique each researcher uses. Furthermore, the composition and properties of chromatin vary from one cell type to the another, during development of a specific cell type, and at different stages in the cell cycle.
3. The DNA – plus – histone – equals – chromatin definition: The DNA double helix in the cell nucleus is packaged by special proteins termed histones. The formed protein/DNA complex is called chromatin. The structural entity of chromatin is the nucleosome.

Nobel Prizes

The following scientists were recognized for their contributions to chromatin research with Nobel Prizes:

See also

• Nucleosome
• Histone-Modifying Enzymes
• Chromosome
• Chromatid

References

Other references

• Corces, V. G. 1995. Chromatin insulators. Keeping enhancers under control. Nature 376:462-463.
• Cremer, T. 1985. Von der Zellenlehre zur Chromosomentheorie: Naturwissenschaftliche Erkenntnis und Theorienwechsel in der frühen Zell- und Vererbungsforschung, Veröffentlichungen aus der Forschungsstelle für Theoretische Pathologie der Heidelberger Akademie der Wissenschaften. Springer-Vlg. , Berlin, Heidelberg.
• Elgin, S. C. R. (ed. ). 1995. Chromatin Structure and Gene Expression, vol. 9. IRL Press, Oxford, New York, Tokyo.
• Gerasimova, T. I. , and V. G. Corces. 1996. Boundary and insulator elements in chromosomes. Current Op. Genet. and Dev. 6:185-192.
• Gerasimova, T. I. , and V. G. Corces. 1998. Polycomb and Trithorax group proteins mediate the function of a chromatin insulator. Cell 92:511-521.
• Gerasimova, T. I. , and V. G. Corces. 2001. CHROMATIN INSULATORS AND BOUNDARIES: Effects on Transcription and Nuclear Organization. Annu Rev Genet 35:193-208.
• Gerasimova, T. I. , K. Byrd, and V. G. Corces. 2000. A chromatin insulator determines the nuclear localization of DNA [In Process Citation]. Mol Cell 6:1025-35.
• Ha, S. C. , K. Lowenhaupt, A. Rich, Y. G. Kim, and K. K. Kim. 2005. Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases. Nature 437:1183-6.
• Pollard, T. , and W. Earnshaw. 2002. Cell Biology. Saunders.
• Saumweber, H. 1987. Arrangement of Chromosomes in Interphase Cell Nuclei, p. 223-234. In W. Hennig (ed. ), Structure and Function of Eucaryotic Chromosomes, vol. 14. Springer-Verlag, Berlin, Heidelberg.
• Sinden, R. R. 2005. Molecular biology: DNA twists and flips. Nature 437:1097-8.
• Van Holde KE. 1989. Year 1989 ( MCMLXXXIX) was a Common year starting on Sunday (link displays 1989 Gregorian calendar) Chromatin. New York: Springer-Verlag. New York ( is a state in the Mid-Atlantic and Northeastern regions of the United States and is the nation's third most populous Springer Science+Business Media or Springer (ˈʃpʁɪŋɐ is a worldwide Publishing company based in Germany, which publishes textbooks academic ISBN 0-387-96694-3.
• Van Holde, K. , J. Zlatanova, G. Arents, and E. Moudrianakis. 1995. Elements of chromatin structure: histones, nucleosomes, and fibres, p. 1-26. In S. C. R. Elgin (ed. ), Chromatin structure and gene expression. IRL Press at Oxford University Press, Oxford.

External links

• Recent chromatin publications and news