Chromatin
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Chromatin is the structural building block of a chromosome. It is found inside the nucleus of a cell and consists of a complex of DNA and protein in eukaryotic cells. The nucleic acids are generally in the form of double-stranded DNA (a double helix). The major proteins involved in chromatin are histone proteins, but other chromosomal proteins are prominent too. DNA is packaged into chromatin thereby constraining the size of the molecule and allowing the cell to control expression of the chromatin-packaged genes. 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 can be made visible by staining, hence its name, which literally means coloured material.
Image:Chromatin chromosome.png
Simplistically, there are three major levels of chromatin organization (Fig. 1):
- nucleosome - "beads on a string"
- 30 nm condensed chromatin fiber consisting of nucleosome arrays in their most compact form
- the hierarchy continues with increasing DNA-packaging density until the metaphase chromosome is attained.
Sperm cell chromatin is an exception to the above. During spermiogenesis, the spermatid's chromatin is remodelled into a more tightly packaged, compact, almost crystal-like structure. This process is associated with the cessation of transcription and involves nuclear protein exchange. The histones are mostly displaced, and replaced by protamines (small, arginine-rich proteins).
There are two types of chromatin: euchromatin and heterochromatin.
Contents |
Levels of Chromatin Organization in Detail
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).
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 fom 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.
The Nucleosome
The basic repeat element of chromatin is the nucleosome. The nucleosome consists of a central protein complex, the histone octamer, and 1.7 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 containing two copies each of H2A, H2B, H3 and H4. Further, there is a linker histone, H1, which contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome together with histone H1 is called a chromatosome.
Beads-On-A-String Chromatosome Array
Chromatosomes, connected by about 20 to 60 base pairs of a continuous linker DNA strand, form a 10 nm "beads-on-a-string" array (Fig. 1-2).
Higher order Chromatin Structure
The higher order structure of the chromatin fiber in the cell is not known in detail. EM studies have demonstrated a fiber with a diameter of 30 nm which is highly dynamic such that it seems to unfold into a 10 nm fiber when transversed by an RNA polymerase engaged in transcription.
Territorial Organization of Chromatin in the Cell Nucleus
Image:Nucleus & Chromatin Territorial Structure.jpg
The diagram (Fig. X) 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).
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).
Chromatin: Alternative Definitions
- Simple & Concise Definition: Chromatin is DNA plus the proteins (and RNA) that package DNA within the cell nucleus.
- 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.
- 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.
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").
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".
See also
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 0387966943.
- 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
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