Nucleosome repeat length

The nucleosome repeat length, (NRL) is the average distance between the centers of neighboring nucleosomes. NRL is an important physical chromatin property that determines its biological function. NRL can be determined genome-wide for the chromatin in a given cell type and state, or locally for a large enough genomic region containing several nucleosomes.^[1]

In chromatin, neighbouring nucleosomes are separated by the linker DNA and in many cases also by the linker histone H1^[2] as well as non-histone proteins. Since the size of the nucleosome is typically fixed (146-147 base pairs), NRL is mostly determined by the size of the linker region between nucleosomes. Alternatively, partial DNA unwrapping from the histone octamer or partial disassembly of the histone octamer can decrease the effective nucleosome size and thus affect NRL.

Past studies going back to 1970s showed that, in general, NRL is different for different species and even for different cell types of the same organism. In addition, recent publications reported NRL variations for different genomic regions of the same cell type.^{[3] [4]} Recent works have compared the NRL around yeast transcription start sites (TSSs) in vivo and that for the reconstituted chromatin on the same DNA sequences in vitro. It was shown that ordered nucleosome positioning arises only in the presence of ATP-dependent chromatin remodeling.^[5] Furthermore, it was reported that the NRL determined around yeast TSSs is an invariant value universal for a given wild type yeast strain, although it can change when one of chromatin remodelers is missing.^[6] In general, NRL depends on the DNA sequence, concentrations of histones and non-histone proteins, as well as long-range interactions between nucleosomes.^[1] NRL determines geometric properties of the nucleosome array, and therefore the higher-order packing of the DNA into the chromatin fiber,^[7] which might affect gene expression.

References

1. Beshnova DA, Cherstvy AG, Vainshtein Y, Teif VB (July 2014). "Regulation of the nucleosome repeat length in vivo by the DNA sequence, protein concentrations and long-range interactions". PLOS Comput. Biol. 10 (2): e1003698. Bibcode:2014PLSCB..10E3698B. doi:10.1371/journal.pcbi.1003698. PMC 4081033. PMID 24992723.
2. Thoma F, Koller T, Klug A (November 1979). "Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin". J. Cell Biol. 83 (2 Pt 1): 403–27. doi:10.1083/jcb.83.2.403. PMC 2111545. PMID 387806.
3. Valouev A, Johnson SM, Boyd SD, Smith CL, Fire A, Sidow A (2011). "Determinants of nucleosome organization in primary human cells". Nature. 474 (7352): 516–520. doi:10.1038/nature10002. PMC 3212987. PMID 21602827.
4. Teif VB; Vainshtein Y; Caudron-Herger M; Mallm JP; Marth C; Höfer T; Rippe K. (21 October 2012). "Genome-wide nucleosome positioning during embryonic stem cell development". Nat Struct Mol Biol. 19 (11): 1185–92. doi:10.1038/nsmb.2419. PMID 23085715. S2CID 34509771.
5. Zhang Z, Wippo CJ, Wal M, Ward E, Korber P, Pugh BF (2011). "A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome". Science. 332 (6032): 977–80. Bibcode:2011Sci...332..977Z. doi:10.1126/science.1200508. PMC 4852979. PMID 21596991.
6. Hennig BP, Bendrin K, Zhou Y, Fischer T (2012). "Chd1 chromatin remodelers maintain nucleosome organization and repress cryptic transcription". EMBO Rep. 13 (11): 997–1003. doi:10.1038/embor.2012.146. PMC 3492713. PMID 23032292.
7. Routh A, Sandin S, Rhodes D (2008). "Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure". Proc Natl Acad Sci U S A. 105 (26): 8872–7. Bibcode:2008PNAS..105.8872R. doi:10.1073/pnas.0802336105. PMC 2440727. PMID 18583476.