Nucleosome

Basic units of chromatin structure

A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins[1] and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.

DNA must be compacted into nucleosomes to fit within the cell nucleus.[2] In addition to nucleosome wrapping, eukaryotic chromatin is further compacted by being folded into a series of more complex structures, eventually forming a chromosome. Each human cell contains about 30 million nucleosomes.[3]

Nucleosomes are thought to carry epigenetically inherited information in the form of covalent modifications of their core histones. Nucleosome positions in the genome are not random, and it is important to know where each nucleosome is located because this determines the accessibility of the DNA to regulatory proteins.[4]

Nucleosomes were first observed as particles in the electron microscope by Don and Ada Olins in 1974,[5] and their existence and structure (as histone octamers surrounded by approximately 200 base pairs of DNA) were proposed by Roger Kornberg.[6][7] The role of the nucleosome as a regulator of transcription was demonstrated by Lorch et al. in vitro[8] in 1987 and by Han and Grunstein[9] and Clark-Adams et al.[10] in vivo in 1988.

The nucleosome core particle consists of approximately 146 base pairs (bp) of DNA[11] wrapped in 1.67 left-handed superhelical turns around a histone octamer, consisting of 2 copies each of the core histones H2A, H2B, H3, and H4.[12] Core particles are connected by stretches of linker DNA, which can be up to about 80 bp long. Technically, a nucleosome is defined as the core particle plus one of these linker regions; however the word is often synonymous with the core particle.[13] Genome-wide nucleosome positioning maps are now available for many model organisms and human cells.[14]

Linker histones such as H1 and its isoforms are involved in chromatin compaction and sit at the base of the nucleosome near the DNA entry and exit binding to the linker region of the DNA.[15] Non-condensed nucleosomes without the linker histone resemble "beads on a string of DNA" under an electron microscope.[16]

In contrast to most eukaryotic cells, mature sperm cells largely use protamines to package their genomic DNA, most likely to achieve an even higher packaging ratio.[17] Histone equivalents and a simplified chromatin structure have also been found in Archaea,[18] suggesting that eukaryotes are not the only organisms that use nucleosomes.

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  5. ^ Olins AL, Olins DE (January 1974). "Spheroid chromatin units (v bodies)". Science. 183 (4122): 330–332. Bibcode:1974Sci...183..330O. doi:10.1126/science.183.4122.330. PMID 4128918. S2CID 83480762.
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  8. ^ Lorch Y, LaPointe JW, Kornberg RD (April 1987). "Nucleosomes inhibit the initiation of transcription but allow chain elongation with the displacement of histones". Cell. 49 (2): 203–210. doi:10.1016/0092-8674(87)90561-7. PMID 3568125. S2CID 21270171.
  9. ^ Han M, Grunstein M (December 1988). "Nucleosome loss activates yeast downstream promoters in vivo". Cell. 55 (6): 1137–1145. doi:10.1016/0092-8674(88)90258-9. PMID 2849508. S2CID 41520634.
  10. ^ Clark-Adams CD, Norris D, Osley MA, Fassler JS, Winston F (February 1988). "Changes in histone gene dosage alter transcription in yeast". Genes & Development. 2 (2): 150–159. doi:10.1101/gad.2.2.150. PMID 2834270.
  11. ^ In different crystals, values of 146 and 147 basepairs were observed
  12. ^ Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (September 1997). "Crystal structure of the nucleosome core particle at 2.8 A resolution". Nature. 389 (6648): 251–260. Bibcode:1997Natur.389..251L. doi:10.1038/38444. PMID 9305837. S2CID 4328827.
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