Nucleosome positioning is involved in many gene regulatory processes happening in the cell, and it may change as cells differentiate or respond to the changing microenvironment in a healthy or diseased organism. One important implication of nucleosome positioning in clinical epigenetics is its use in the “nucleosomics” analysis of cell-free DNA (cfDNA) for the purpose of patient diagnostics in liquid biopsies. The rationale for this is that the apoptotic nucleases that digest chromatin of the dying cells mostly cut DNA between nucleosomes. Thus, the short pieces of DNA in body fluids reflect the positions of nucleosomes in the cells of origin. Here, we report a systematic nucleosomics database — NucPosDB — curating published nucleosome positioning datasets in vivo as well as datasets of sequenced cell-free DNA (cfDNA) that reflect nucleosome positioning in situ in the cells of origin. Users can select subsets of the database by a number of criteria and then obtain raw or processed data. NucPosDB also reports the originally determined regions with stable nucleosome occupancy across several individuals with a given condition. An additional section provides a catalogue of computational tools for the analysis of nucleosome positioning or cfDNA experiments and theoretical algorithms for the prediction of nucleosome positioning preferences from DNA sequence. We provide an overview of the field, describe the structure of the database in this context, and demonstrate data variability using examples of different medical conditions. NucPosDB is useful both for the analysis of fundamental gene regulation processes and the training of computational models for patient diagnostics based on cfDNA. The database currently curates ~ 400 publications on nucleosome positioning in cell lines and in situ as well as cfDNA from > 10,000 patients and healthy volunteers. For open-access cfDNA datasets as well as key MNase-seq datasets in human cells, NucPosDB allows downloading processed mapped data in addition to the regions with stable nucleosome occupancy. NucPosDB is available at https://generegulation.org/nucposdb/.

Nucleosome repositioning in cancer highlights changes of many aspects of genome organisation and regulation. Understanding it is important both from the fundamental point of view and for medical diagnostics based on cell-free DNA (cfDNA), which originates from genomic DNA regions protected from digestion by nucleosomes. Here we generated ultra-high resolution nucleosome maps in paired tumour and normal tissues from the same breast cancer patients using MNase-assisted histone H3 ChIP-seq and compared them with the corresponding cfDNA from blood plasma. We detected cancer-specific single-nucleosome repositioning at key regulatory regions in a patient-specific manner, as well as common patterns across patients. The nucleosomes gained in tumour versus normal tissue were particularly informative of cancer pathways, with 20-fold enrichment at CpG islands, a large fraction of which marked promoters of genes encoding DNA-binding proteins. Tumour tissues were characterised by 5-10 bp decrease in average distances between nucleosomes (nucleosome repeat length, NRL). These effects were modulated by GC content and DNA sequence repeats and correlated with differential DNA methylation and binding of linker histone variants H1.4 and H1X. Our findings provide missing mechanistic understanding of nucleosome positioning in tumour tissues and can be valuable for nucleosomics analyses in liquid biopsies.

Nucleosome positioning is involved in many gene regulatory processes happening in the cell and it may change as cells differentiate or respond to the changing microenvironment in a healthy or diseased organism. One important implication of nucleosome positioning in clinical epigenetics is its use in the “nucleosomics” analysis of cell-free DNA (cfDNA) for the purpose of patient diagnostics in liquid biopsies. The rationale for this is that the apoptotic nucleases that digest chromatin of the dying cells mostly cut DNA between nucleosomes. Thus, the short pieces of DNA in body fluids reflect the positions of nucleosomes in the cells of origin. Here we report a systematic nucleosomics database – NucPosDB, curating published nucleosome positioning datasets in vivo as well as datasets of sequenced cell-free DNA (cfDNA) that reflect nucleosome positioning in situ in the cells of origin. Users can select subsets of the database by a number of criteria and then obtain raw or processed data. NucPosDB also reports the originally determined regions with stable nucleosome occupancy across several individuals with a given condition. An additional section provides a catalogue of computational tools for the analysis of nucleosome positioning or cfDNA experiments and theoretical algorithms for the prediction of nucleosome positioning from DNA sequence. We provide an overview of the field, describe the structure of the database in this context and demonstrate data variability using examples of different medical conditions. NucPosDB is useful both for analysis of fundamental gene regulation processes and training computational models for patient diagnostics based on cfDNA. The database currently curates ∼400 publications on nucleosome positioning in cell lines and in situ as well as cfDNA from >10,000 patients and healthy volunteers. For open-access cfDNA datasets as well as key MNase-seq datasets in human cells, NucPosDB allows downloading processed mapped data in addition to the stable-nucleosome regions. NucPosDB is available at https://generegulation.org/nucposdb/.