# Nucleosome spacing across cell types, diseases, and ages

**Authors:** Milena Bikova, Christopher T Clarkson, Vladimir B Teif

PMC · DOI: 10.1093/nar/gkag074 · 2026-03-05

## TL;DR

The paper explores how nucleosome spacing varies across cell types, diseases, and ages, linking these patterns to gene activity and health.

## Contribution

The paper offers a critical analysis of nucleosome spacing patterns and their biological implications across diverse genomic contexts.

## Key findings

- Active genomic regions have shorter nucleosome spacing compared to inactive regions.
- Cancer cells show shorter nucleosome spacing than normal cells of the same type.
- Nucleosome spacing increases with aging.

## Abstract

Nucleosome spacing patterns in the genome form a unique signature of a given cell, reflecting its chromatin organization and gene expression. Recently, studies of nucleosome spacing have expanded substantially due to the development of novel experimental tools and increased analysis of human samples. This has yielded thousands of high-resolution nucleosome maps across many species and cell types, as well as multiple human datasets that span across different ages and health conditions. With the rapid increase in nucleosome mapping data, their analysis and interpretation have become critically important. Indeed, several discrepancies in nucleosome spacing have been reported recently, using different experimental methods. However, when nucleosome spacing is consistently analysed, it can be linked to biologically important processes: (i) active genomic regions are characterized by shorter distances between nucleosomes in comparison to inactive regions; (ii) cancer cells tend to have shorter distances in comparison to normal cells of the same type; and (iii) ageing usually increases distances between nucleosomes. In many cases, the underlying molecular mechanisms remain to be clarified. Here, we provide a critical analysis of this field, focusing on nucleosome spacing in different types of genomic regions and cell types, as well as changes in cell differentiation, cancer, and ageing.

Graphical Abstract

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Mecp2 (methyl CpG binding protein 2) [NCBI Gene 17257] {aka 1500041B07Rik, D630021H01Rik, Mbd5, WBP10}, NRL (neural retina leucine zipper) [NCBI Gene 4901] {aka D14S46E, ESCS2, NRL-MAF, RP27}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, CHD1 (chromodomain helicase DNA binding protein 1) [NCBI Gene 1105] {aka CHD-1, PILBOS}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, H2AC18 (H2A clustered histone 18) [NCBI Gene 8337] {aka H2A, H2A.2, H2A/O, H2A/q, H2AFO, H2a-615}, H1-4 (H1.4 linker histone, cluster member) [NCBI Gene 3008] {aka H1.4, H1E, H1F4, H1s-4, HIST1H1E, RMNS}, CENPA (centromere protein A) [NCBI Gene 1058] {aka CENP-A, CenH3}, SMARCA5 (SNF2 related chromatin remodeling ATPase 5) [NCBI Gene 8467] {aka ISWI, SNF2H, WCRF135, hISWI, hSNF2H}, CTCF (CCCTC-binding factor) [NCBI Gene 10664] {aka CFAP108, FAP108, MRD21}, CHD4 (chromodomain helicase DNA binding protein 4) [NCBI Gene 1108] {aka CHD-4, Mi-2b, Mi2-BETA, SIHIWES}, Nrl (neural retina leucine zipper gene) [NCBI Gene 18185] {aka D14H14S46E}, KDM5B (lysine demethylase 5B) [NCBI Gene 10765] {aka CT31, JARID1B, MRT65, PLU-1, PLU1, PPP1R98}, H2AZ1 (H2A.Z variant histone 1) [NCBI Gene 3015] {aka H2A.Z-1, H2A.z, H2A/z, H2AFZ, H2AZ}, H2BC21 (H2B clustered histone 21) [NCBI Gene 8349] {aka GL105, H2B, H2B-GL105, H2B.1, H2BE, H2BFQ}, H1-10 (H1.10 linker histone) [NCBI Gene 8971] {aka H1.10, H1FX, H1X}, CENPC (centromere protein C) [NCBI Gene 1060] {aka CENP-C, CENPC1, MIF2, hcp-4}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}
- **Diseases:** Bowel Cancer (MESH:D009369), CLL (MESH:D015461), neurodegenerative diseases (MESH:D019636), Pancreatic Cancer (MESH:D010190), myeloid leukemia (MESH:D007951), Neuromuscular Diseases (MESH:D009468), blood cancers (MESH:D019337), malaria (MESH:D008288), breast cancer (MESH:D001943), lymphomas (MESH:D008223)
- **Chemicals:** dA (MESH:C025953), DFF (-), hydroxyl radicals (MESH:D017665), ATP (MESH:D000255), polyamines (MESH:D011073)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Schizosaccharomyces pombe (fission yeast, species) [taxon 4896], Gallus gallus (bantam, species) [taxon 9031], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), ESCs — Mus musculus (Mouse), Embryonic stem cell (CVCL_9108)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961432/full.md

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Source: https://tomesphere.com/paper/PMC12961432