Fig. 1

The study design and small-scale nucleosome repositioning analysis. A Scheme of the study: paired tumour/normal breast tissues taken from breast cancer patients numbered P1–P4 were used to determine nucleosome positioning using MNase-seq and MNase-assisted histone H3 ChIP-seq (MNase-H3), complemented by whole-genome sequencing of cell-free DNA extracted from blood plasma from the same patients. The analysis of each sample was performed individually, without pooling. B Example genomic region (Chr 17: 7,855,262–7,592,516) enclosing gene TP53 and nucleosome occupancy maps for patient P3. Tracks top to bottom: normal tissue MNase-H3 and MNase-seq; tumour tissue MNase-H3 and MNase-seq; cfDNA in two replicates; UCSC Genome Browser track with ENCODE Factorbook TF motifs. Rectangles show regions containing common (brown), gained (green) and shifted nucleosomes (violet). The gained and shifted classifications are not mutually exclusive. C Fold enrichment of nucleosomes that were gained and lost in all tumours versus healthy breast tissues in CpG islands, promoters, CTCF binding sites, L1 repeats and Alu repeats, in comparison with the intersections with these regions expected by chance. In all cases except for nucleosomes lost in BRC at CTCF sites, enrichments are statistically significant (p < 0.005, Fisher test). D–F Representative nucleosome occupancy profiles around TF binding sites. D and E Nucleosome profiles in patient P1 (top) and patient P3 from the current cohort (bottom) around ERα sites bound in any three out of six ER-positive BRC patients from the cohort of Severson et al., 2018 (D) and in sites bound by ERα in all six BRC patients from Severson et al., 2018 (E) (10-bp smoothing). F Nucleosome profiles in patient P1 (top) and patient P3 (bottom) around FOSL2 binding sites determined in MCF-7 cells. Black lines—tumour tissues; red—normal tissues; blue—cfDNA from the same patient