3rd year PhD student at Ferreira lab, St Andrews
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ALT Figure 5 from Jacob et al, 2024. NRL shortening as a novel breast cancer marker. A–E) NRL values calculated for each individual sample from this study inside different types of genomic regions. A) Transcriptionally active A-compartments of chromatin annotated in breast cancer MCF-7 cells; B) Regions surrounding gene promoters. C Genomic regions around Alu repeats; D) Regions enriched with H1X linker histones in breast cancer T47D cells; E) Differentially methylated DNA regions annotated based on cell lines MCF-10A, MCF-7 and MDA-MB-231. Open squares—average NRL values for a given condition; horizontal lines—median values. The colours of the points are assigned per sample as in Fig. 3A. F) A scheme of the change of nucleosome compaction in breast cancer tissues. DNA (black) is wrapped around histone octamers (grey) in contact with linker histones (blue). MNase used in this study or apoptotic nucleases present in situ (orange) cut DNA not protected by nucleosomes and linker histones.
ALT 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
ALT Nucleosome repeat length shortening in cancer. A Frequencies of distances between dyads of DNA fragments protected from MNase digestion in paired normal and tumour breast tissue samples from patient P2. B Genome-wide NRL values calculated for each sample reported in this study. The difference of NRLs between normal and tumour tissues is statistically significant (p = 0.014, paired sample t test). Open squares—average values across all samples in a given condition; horizontal lines—median values for a given condition. The colours of the points corresponding to NRL values in N/T tissues are assigned per patient and per experiment type as follows: MNase-seq: patient P1 (black), P2 (red), P3 (blue), P4 (green); MNase-assisted H3 ChIP-seq: patient P1 (violet), P3 (brown), P4 (cyan). Panels A and B use DNA fragments of sizes 120–180 bp. C NRL in normal (grey violins) and tumour (beige violins) breast tissue calculated inside genomic regions enriched with 160–180 bp DNA fragments (“long nuc”)
![Effects of linker histones on nucleosome repositioning in breast cancer. A Correlation of GC content and H1 occupancy in 10-kb regions genome-wide. H1 variants H1.0, H1.2 and H1.5 preferentially bind AT-rich regions, while H1.4 and H1X have a higher affinity for GC-rich regions. B–D Averaged aggregate profiles of H1 occupancy around different types of DNA fragments protected from MNase digestion. These profiles were first calculated individually for each MNase-seq tumour tissue sample reported in this study, and then averaged across all patients. B Occupancy of H1 variants around nucleosome dyads calculated for different DNA fragment sizes. C H1 occupancy in the region [-50, 50] bp around nucleosome dyad calculated for different H1 variants as a function of DNA fragment size. D Average H1X occupancy in T47D breast cancer cell line calculated around DNA fragments of 160–180 bp in normal (black lines) and tumour breast tissues (red). E Average H1X occupancy profiles...](https://pbs.twimg.com/media/GKK2oq5WoAAD6AP.jpg?name=orig)
ALT Effects of linker histones on nucleosome repositioning in breast cancer. A Correlation of GC content and H1 occupancy in 10-kb regions genome-wide. H1 variants H1.0, H1.2 and H1.5 preferentially bind AT-rich regions, while H1.4 and H1X have a higher affinity for GC-rich regions. B–D Averaged aggregate profiles of H1 occupancy around different types of DNA fragments protected from MNase digestion. These profiles were first calculated individually for each MNase-seq tumour tissue sample reported in this study, and then averaged across all patients. B Occupancy of H1 variants around nucleosome dyads calculated for different DNA fragment sizes. C H1 occupancy in the region [-50, 50] bp around nucleosome dyad calculated for different H1 variants as a function of DNA fragment size. D Average H1X occupancy in T47D breast cancer cell line calculated around DNA fragments of 160–180 bp in normal (black lines) and tumour breast tissues (red). E Average H1X occupancy profiles...
ALT NRL shortening as a novel breast cancer marker. A–E NRL values calculated for each individual sample from this study inside different types of genomic regions. A Transcriptionally active A-compartments of chromatin annotated in breast cancer MCF-7 cells; B Regions surrounding gene promoters. C Genomic regions around Alu repeats; D Regions enriched with H1X linker histones in breast cancer T47D cells; E Differentially methylated DNA regions annotated based on cell lines MCF-10A, MCF-7 and MDA-MB-231. Open squares—average NRL values for a given condition; horizontal lines—median values. The colours of the points are assigned per sample as in Fig. 3A. F A scheme of the global change of nucleosome compaction in breast cancer tissues. DNA (black) is wrapped around histone octamers (grey) in contact with linker histones (blue). MNase used in this study or apoptotic nucleases present in situ (orange) cut DNA not protected by nucleosomes and linker histones. Cancer cells have shorter NRL...
ALT A woman in a lab coat and gloves working in a laboratory.
ALT “We’re thrilled that government has announced £45 million to support charity-funded early career researchers. This recognises the vital role that charities play in nurturing research careers and supporting the people who will unlock new ways to save and improve lives. The funding will make a huge difference to AMRC members as they continue to recover post-pandemic.”
ALT A photo of Professor Philippa Saunders FMedSci, speaking at an event. A banner that reads 'Developing talented researchers' can be seen in the background.
ALT "The Starter Grant enabled me to design a new exciting research project, gain experience in grant writing, and then drive the project myself with the support of an experienced supervisor and a strong research group." Abbe Crawford 2018 Starter Grant awardee
ALT Left image: A person standing in front of a research poster talking about their work to an audience. Right image: Two people sitting at a table chatting and smiling.
ALT The adventure of our cartoon personages started in 2019 on the cover of Genome Research, associated with our article which showed that CTCF can set boundaries for one-dimensional DNA methylation spreading in chromatin. Wiehle L., Thorn G.J., Raddatz G., Clarkson C.T., Rippe K., Lyko F., Breiling A., Teif V.B. (2019) DNA (de)methylation in embryonic stem cells controls CTCF-dependent chromatin boundaries. Genome Research 29, 750-761
ALT In our recent Nature Communications article (Thorn et al., 2022) we developed a framework ChromHL allowing to predict from DNA sequence and protein concentrations the locations of such chromatin nanodomains (e.g. H3K9me2/3 associated heterochromatin). The DNA sequence sets the map of potential locations of nanodomains through motifs of transcription factors that can initiate and stop nanodomain spreading. The abundance of chromatin proteins such as HP1, which changes during cell differentiation refines the sequence-determined thermodynamic landscape of chromatin domains. Thorn G.J., Clarkson C.T., Rademacher A., Mamayusupova H., Schotta G., Rippe K. and Teif V.B. (2022) DNA sequence-dependent formation of heterochromatin nanodomains. Nature Communications 13, 1861
ALT Another concept of chromatin organisation was introduced in our Nucleic Acids Research article (Clarkson et al., 2019). Distances between nucleosomes decrease near chromatin boundaries and this is affected by cell differentiation. Chromatin remodellers (mice on the cartoon) are “measuring” distances between nucleosomes (bushes on the cartoon), while the anchors for such measurements are provided by CTCF proteins. Clarkson C.T., Deeks E.A., Samarista R., Mamayusupova H., Zhurkin V.B., Teif V.B. (2019) CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length. Nucleic Acids Res 47, 11181-11196.
ALT The latest cartoon in this series is associated with our theoretical biophysical paper (Hedley et al., 2021), which showed that nucleosome arrays with different distances between nucleosomes can recognise each other. The interaction forces between such differently arranged nucleosome arrays are very weak, but because they accumulate over large distances this effect may become significant, especially in areas of ordered chromatin sections such as DNA sequence repeats, near CTCF sites, etc. We liked this last cartoon so much that it currently serves as our “official” lab photo :). Hedley J.G., Teif V.B. and Kornyshev A.A. (2021) Nucleosome induced homology recognition in chromatin. J. Royal Soc. Interface 18, 20210147.
