Chromatin

From Encyclopedia Jr, free information reference for Kids

Chromatin is the complex of DNA and protein found inside the nuclei of eukaryotic cells. The nucleic acids are in the form of double-stranded DNA (a double helix). The major proteins involved in chromatin are histone proteins, although many other chromosomal proteins are have prominent roles too. The purposes 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 as a mechanism to control expression. Changes in chromatin structure are affected mainly by methylation (DNA and proteins) and acetylation (proteins). Chromatin structure is also relevant to DNA replication and DNA repair.

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

Fig. 1: Levels of DNA condensation. (1) DNA double-strand helix. (2) Chromatin strand (DNA with histones). (3) Condensed chromatin during interphase with centromere. (4) Condensed chromatin during prophase. (Two copies of the DNA molecule are now present) (5) Chromosome during metaphase.

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

1. DNA wrapping around nucleosomes - The "beads on a string" structure.
2. A 30 nm condensed chromatin fiber consisting of nucleosome arrays in their most compact form.
3. Higher level DNA packaging into the metaphase chromosome.

These structures are not found in all eukaryotic cells, there are examples of more extreme packaging, for example sperm cells and avian red blood cells.

The different levels of chromatin compaction are clearly visible in cells. In non-dividing cells there are two types of chromatin: euchromatin and heterochromatin. These correspond to uncompacted actively transcribed DNA and compacted untranscribed DNA.

[edit] Levels of Chromatin Organization

[edit] DNA structure

Fig. 2: Alternative structural forms of DNA influencing chromatin structure

[edit] Chromatin & Watson/Crick base pairing

Crick and Watson's famous structure of DNA (called B-DNA) is only one of three possible structural forms (Fig. 2).

For the C-N bond between a base and its sugar there are two different conformations. The anti-conformation occurs in all A- and B-DNAs as well as in Z-DNA where a Cytosine is present. In case of a Guanine Z-DNA takes the syn-conformation. The periodic change between a purine and pyrimidine along the strand of a Z-DNA accomplishes the alternating syn-anti-conformation characteristic of the zigzag structure of the Z-DNA helix. The yellow circles designated A, B, Z indicate the axes of the three possible types of DNA (Fig. 2).

Fig. 3: Structure of DNA with two B-Z DNA junctions: It encompasses 1. breakage of a hydrogen-bond, where a Guanine rotates around its glycosyl-bond and the sugar thereby transforms into its syn-conformation. 2. Rotation of the corresponding second base (Cytosine) involving rotation of the sugar around the sugar-phosphate-bond. 3. At the B-Z junction hydrogen-bonds remain broken and bases are extruded.

[edit] Junction between B- and Z-DNA

Chromatin regions near the transcription start site frequently contain DNA sequence motifs favourable for forming Z-DNA. Likewise, formation of Z-DNA near the promoter region stimulates transcription. Z-DNA is stabilized by binding specific proteins. Formation of Z-DNA from B-DNA is a dynamic process where B-DNA is the relaxed state. When a Z-DNA segment is formed two B-Z junctions form (Fig.3). The crystal structure of such junctions is known. At each junction the hydrogen bonds between a Watson/Crick base-pair is broken and the bases are extruded. Extrusion of a base from the helix is a well-known reaction performed by enzymes (i.e. DNA glycosylase) that edit or repair DNA during Base Excision Repair (BER). Crystal structures of extruded bases co-crystallized with Hha1 methyltransferase, human DNA repair protein AGT(O(6)-alkylguanine-DNAalkyltransferase), or bacteriophage T4 endonuclease V are similar to the extruded bases at B-Z junctions. Z-DNA may also provide a sink to absorb torsional strain following an RNA polymerase or a transient nucleosome. Also Z-DNA may represent a signal for the recruitment of RNA-editing enzymes. It is possible that chromatin encompassing Z-DNA segments also affect replication.

[edit] The Nucleosome and "Beads-on-a-String"

Main articles: Nucleosome, Chromatosome and Histone

A cartoon representation of the nucleosome structure. From PDB 1KX5.

The basic repeat element of chromatin is the nucleosome, linked by sections of linker DNA. The nucleosome consists of 1.65 turns of DNA (about 146 base pairs), which are wrapped around the histone octamer complex. There are four different types of core histone proteins which form the octamer, which is made up of two copies each of H2A, H2B, H3 and H4. The small diameter (~10nm) around which the DNA bends is far smaller than can be reached by 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 10nm "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 (A) and tyrosine (T) bases are more favorably compressed into the inner minor grooves. 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.

[edit] 30nm 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 30nm 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 the exact structure. There are, however, three well established models.

This level of chromatin structure is thought to be the form of euchromatin, which contains actively transcribed genes. EM studies have demonstrated the 30nm fibre is highly dynamic such that it unfold into a 10nm fiber ("beads-on-a-string") structure when transversed by an RNA polymerase engaged in transcription.

The three models are based on the accepted facts that the nucleosomes lie perpendicular to the axis of the fibre, the linker histones lie on the inside of the structure and that it readily unwinds into the 10nm "beads-on-a-string" fibre.

[edit] Territorial Organization of Chromatin in the Cell Nucleus

Fig. 4: Hypothetical Model of the Territorial Organization of Chromatin in the Cell Nucleus

The diagram (Fig. 4) represents a model of a cell (gray oval) with a nucleus (dark gray oval). Two chromosomes are shown as chromatin fibers (yellow and red lines). Proteins are represented as small ovals.

Note the association of the chromatin components with the nuclear membrane. Chromosomes are territorially interlinked by chromatin protein complexes (scaffold proteins see above).

[edit] 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

Enzymes associated with chromatin are those involved in DNA replication and repair, in transcription, and in post-translational modification of histones. Examples are various types of nucleases and proteases. Scaffold proteins encompass chromatin proteins such as insulators, domain boundary factors and cellular memory modules (CMMs).

[edit] Chromatin: Alternative Definitions

1. Simple & 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.

[edit] History

In 1882 Walther Flemming used the term Chromatin for the first time. Flemming assumed that within the nucleus there was some kind of a nuclear-scaffold. Further there were nucleoli, the nuclear plasm and the nuclear membranes. He wrote (transl. from German): “The scaffold owes its capability of refraction, the way how it behaves, and in particular its colorability to a substance which, with regard to its latter attribute, I have termed Chromatin. It is possible that this substance is really identical with the Nuclein-bodies. .... I’ll retain the name Chromatin as long as Chemistry has decided about it, and I empirically refer to it as that substance in the cell's nucleus which takes up the dye upon staining the nucleus ("Kerntinktionen").

[edit] Nobel Prizes Related to Chromatin

Albrecht Kossel (University of Heidelberg) was awarded the Nobel Prize in Physiology or Medicine 1910 "in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances".

Thomas Hunt Morgan (California Institute of Technology) was awarded the Nobel Prize in Physiology or Medicine 1933 "for his discoveries concerning the role played by the chromosome in heredity".

Francis Crick, James Watson, Maurice Wilkins (MRC Laboratory of Molecular Biology, Harvard University, London University) were awarded the Nobel Prize in Physiology or Medicine 1962 "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

Aaron Klug (MRC Laboratory of Molecular Biology) was awarded the Nobel Prize in Chemistry 1982 "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes".

[edit] See also

• Chromosome
• Chromatid
• Genetics
• Nucleosome
• bookmarking

[edit] 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. Chromatin. New York: Springer-Verlag. 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.

[edit] External links

• Recent chromatin publications and news
• Epigenome Network of Excellence (NoE)