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teiflab.bsky.social
Teif lab
@teiflab.bsky.social
2.9K followers 1K following 300 posts
Teif lab at the University of Essex. We work on gene regulation in chromatin and applications to liquid biopsies, using approaches of genomics, biophysics, bioinformatics & AI. Our focus is nucleosomics, TF binding, CTCF, cfDNA. https://generegulation.org
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teiflab.bsky.social
Maansson et al., 2025. Liquid biopsy epigenetics: establishing a molecular profile based on cell-free DNA [review] febs.onlinelibrary.wiley.com/doi/full/10....
Various analytes of liquid biopsies. Cancer cells shed various analytes into the bloodstream, all of which can be analyzed in liquid biopsies. (A) Extracellular vesicles contain various molecules, including DNA, RNA, and proteins representing the biology of the tumor. (B) Several types of cell-free RNA (cfRNA) molecules can be found in plasma, including noncoding micro-RNA (miRNA), long noncoding RNA (lncRNA), messenger RNA (mRNA), and tumor-derived RNA fusions. (C) Circulating tumor cells (CTCs) from primary tumors or metastatic sites directly represent cancer biology at the site of origin. CTCs can group together with healthy cells, creating CTC clusters. (D) Many features of cell-free DNA (cfDNA) provide great insights into tumor biology. These features include fragmentomics focusing on cfDNA fragment lengths and fragment end motifs (FEMs), 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) patterns and post-translational modifications (PTMs) of circulating histones. In addition, somatic variants, such as single-nucleotide variants (SNVs), insertions and deletions (indels), and copy number alterations (CNAs) are detectable in liquid biopsies. Origin of cell-free DNA (cfDNA) in healthy individuals and various diseases. (A) In a healthy population, the tissue of origin of cfDNA can be traced to hematopoietic (90%) and nonhematopoietic cells (10%). Of circulating peripheral blood mononuclear cells (PBMCs), monocytes (yellow) and granulocytes (green) are the main contributors to the cfDNA pool. Erythroblasts (pink) and megakaryocytes (blue) are the main contributors from the bone marrow. Nonhematopoietic cfDNA primarily originates from endothelial and liver cells (red). (B, C) Pathological conditions can alter the origin of cfDNA; however, most of the cfDNA still originates from healthy tissues shown in (A) (gray). Patients with acute myocardial infarction (AMI) have increased cfDNA from cardiac (purple) cells (B). Similarly, cancer patients have an increased fraction of cfDNA from the organ of the primary tumor and the metastatic site (C). This is illustrated with an increased fraction of colon (orange) and neuron (brown) cfDNA in a colorectal cancer (CRC) patient with a brain metastasis. Different cell-free DNA (cfDNA) methylation detection methods. (A) Normal and tumor cells have different methylation profiles, which are detectable in the bloodstream. Several strategies for cfDNA methylation quantification exist, each with their own strengths (+) and limitations (−). (B) Bisulfite conversion is the gold standard of methylation profiling; however, it is limited by high DNA degradation requiring a high input content. (C) As an alternative to bisulfite, enzymatic methyl sequencing (EM-seq) preserves the DNA integrity while providing single base-pair (bp) resolution of 5-methylcytosine (5mC) with higher coverage and less GC bias than bisulfite conversion. (D) Two separate 5mC cfDNA enrichment strategies exist, cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP–seq) and T7-MBD-seq. cfMeDIP utilizes anti-5mC-DNA antibodies to isolate methylated cfDNA fragments, whereas T7-MBD-seq uses methyl-binding domain 2 protein (MBD2) to enrich for 5mC. Precipitated cfDNA is sequenced, generating a coverage profile representing the genomic region's methylation status. (E) 6-letter sequencing with Duet is one of the more recently developed methods and enables quantification of 5mC and 5-hydroxymethylcytosine (5hmC) at single-bp resolution. (F) Native cfDNA is sequenced with long reads using nanopore technology, generating both an epigenetic and genetic profile at single-bp resolution. Fragmentomics of active and inactive genes. (A) Stable regions in the genome result in cell-free DNA (cfDNA) coverage peaks and valleys corresponding to the underlying chromatin structure. Regions with more dynamic chromatin result in a flatter cfDNA coverage profile. (B) Inactive genes are enriched for 5-methylcytosine (5mC) and do not have a structured cfDNA coverage profile around the transcript start site (TSS). cfDNA fragments from inactive genes have a peak at approximately 165 bp corresponding to caspase-activated DNase (CAD) cleavage in internucleosomal regions, leading to distinct fragment end motifs (FEMs). (C) Active genes are depleted of nucleosomes around the TSS, leading to distinct cfDNA coverage profiles. cfDNA fragments from active genes are shorter, with approximately 10-bp oscillations. Gene activity is also characterized by hypomethylation, causing the DNA to be more loosely bound to the nucleosome, allowing for internucleosomal CAD cleavage and altered FEM frequencies.
November 24, 2025 at 11:24 AM
teiflab.bsky.social
Some refs on nucleosome-mediated cooperativity in TF binding:
▶️Concept suggested by Polach & Widom, 1996: www.sciencedirect.com/science/arti...
▶️Our first single-bp resolution model, 2010: www.cell.com/biophysj/ful...
▶️Its application to TFs at enhancers, 2011: iopscience.iop.org/article/10.1...
November 24, 2025 at 10:21 AM
teiflab.bsky.social
Congratulations to Amishasingh Beeharry for successfully passing the MSD viva! You are the best, Amisha! Thank you very much to the examiners, Abdenour Soufi and Toni Marco!
November 18, 2025 at 4:20 PM
teiflab.bsky.social
October 31, 2025 at 4:45 PM
teiflab.bsky.social
Bercovich et al., 2025. IceQream: Quantitative chromosome accessibility analysis using physical TF models www.nature.com/articles/s41...
▶️spatially integrates sequences and localises them relative to the target locus
▶️infers effective TF concentrations
▶️supplements with pairwise TF interactions
Schematic of the IceQream (IQ) workflow: (i) Single-cell ATAC raw counts are transformed into estimated access probabilities (AP). (ii) The IQ model incorporates transcription factor (TF) models, epigenomic context variables, and pairwise interactions of TF models. Each TF model integrates contributions from strong and weak affinity sequences, weighted by spatial preferences around the accessible hotspot, which are transformed into dose-response-like spatial binding preference curves using pre-defined non-linear functions. (iii) Model initialization involves scanning candidate TF models from PSSM (position-specific scoring matrix) databases and de novo motif regression. (iv) An integrated IQ model predicts differential AP (dAP) across a selected manifold trajectory. (v) IQ models from multiple trajectories are fused to create a manifold-wide set of common TF motif models.
October 26, 2025 at 2:25 PM
teiflab.bsky.social
It seems that it was not introduced by Google Scholar. It is a third-party add-on
project.iith.ac.in/sharmaglab/g...
addons.mozilla.org/en-US/firefo...
October 26, 2025 at 10:56 AM
teiflab.bsky.social
October 16, 2025 at 11:34 AM
teiflab.bsky.social
This is consistent with our observations, where in many cases statistically significant (and biologically informative) differences that occur between different states are just about 1-2bp or few bps that do not round to 5 (e.g. figure below from Piroeva et al., 2023) genome.cshlp.org/content/33/1...
October 7, 2025 at 9:43 AM
teiflab.bsky.social
When NRL is defined as a single genome-average value, it is usually not expected to be quantized. For example, this distribution of linker sizes from Voong et al, 2006 shows 10-bp quantization of preferred sizes, but the average of this distribution is expected to be a non-quantized value.
October 7, 2025 at 9:35 AM
teiflab.bsky.social
October 6, 2025 at 2:56 PM
teiflab.bsky.social
IT as a whole may be moved just about 100% up on this graph, but a sub-sector devoted to AI moved about 1000% up, so it might be interesting to repeat that earnings vs valuations analysis specifically for AI companies.
October 6, 2025 at 11:24 AM
teiflab.bsky.social
Interesting paper from Gernot Längst & Co. They calculated nucleosome repeat length in Plasmodium falciparum, the malaria-causing parasite, and showed that it follows a smooth continuous function of time (the numbers on the X axis below are hours post-invasion) www.biorxiv.org/content/10.1...
October 4, 2025 at 7:01 PM
teiflab.bsky.social
Polletti et al, 2025. Control of myeloid lineage fidelity and response to stimuli by ISWI-enforced nucleosome phasing www.cell.com/immunity/abs...

▶️PU.1 can form strongly phased nucleosome arrays similar to CTCF
September 28, 2025 at 1:29 PM
teiflab.bsky.social
Aging by the clock and yet without a program [perspective by David Meyer, Alexei Maklakov & Björn Schumacher] www.nature.com/articles/s43...
September 19, 2025 at 10:45 AM
teiflab.bsky.social
Hsu et al., 2025. MNase stratification reveals heterogeneous 5hmC in naive B cells www.biorxiv.org/content/10.1...
September 16, 2025 at 8:21 AM
teiflab.bsky.social
my target price remains 200 for this one
September 8, 2025 at 7:05 PM
teiflab.bsky.social
Contributions of local structural and energetic features of DNA to large-scale genomic organization [perspective by Wilma Olson & Co) www.sciencedirect.com/science/arti...
Oscillatory pattern of chain extension and nucleosome self-association with variation in protein-free DNA linker length in simulated nucleosome-decorated DNA chains. Regular structures bearing 15 nucleosomes constructed from the mean rigid-body parameters between successive base pairs; nucleosomal cores depicted as wedge-shaped objects and color-coded to highlight the two- and three-start organization of the structures. Nucleosomal DNA constrained to the 147-bp pathway found in the best-resolved core particle structure, pdb_id 1kx5 Distortions in the average structures of simulated nucleosome-decorated DNA chains introduced by changes in the positioning of a singe nucleosome. A. Local opening and unpacking of a compact array introduced by a single 2-bp increment in the spacing between nucleosomes. B. Kinking of an extended array by a single 5-bp increment in nucleosome spacing. Effects of the nucleosomal DNA pathway on the average configurations of simulated 12-nucleosome arrays. Average structures bearing the undertwisted DNA found in the best-resolved core particle structure, pdb_id 1kx5, compared to the overtwisted DNA found in the RCC1-nucleosome complex, pdb_id 3mvd. The regulatory protein is not included in the simulations. Upper views looking perpendicular to the chromatin axis and lower views down the axis Molecular 'snapshots' illustrating the potential effects of chain length and nucleosome positioning on large-scale chromatin folding. A. Smoothly deformed array of 78 nucleosomes with uniform 177-bp spacing. B. 77-nucleosome chromatin 'copolymer' containing three stretches of nucleosomes with different spacings: a compact array of 26 nucleosomes (deep brown) with 172-bp spacing at the 5́-end of the chain; an extended array of 26 nucleosomes (light brown) with 177-bp spacing in the middle; an opened array of 25 nucleosomes (yellow) with 207-bp spacing and a nucleosome-free gap at the 3́-end of the chain. Note the more pronounced junction between ‘helical’ stretches when the spacing changes by roughly a half turn of DNA (172 – 177 = –5 bp) than when altered by a multiple of the double-helical repeat (207 – 177 = 30 bp). The presence of a nucleosome-free gap, within the stretch of nucleosomes spaced at 207-bp intervals, enhances the flexibility of the modeled structure, allowing the chain to bend in various directions
August 23, 2025 at 11:33 AM
teiflab.bsky.social
Saunders et al., 2025. HMGB1 deforms nucleosomal DNA to generate a dynamic chromatin environment counteracting the effects of linker histone www.science.org/doi/full/10....
▶️HMGB1 sites are away from where H1 binds
▶️HMGB1 increases nucleosomal DNA accessibility without displacing H1
August 19, 2025 at 9:43 AM
teiflab.bsky.social
Liu et al., 2025. An automated ATAC-seq method reveals sequence determinants of transcription factor dose response in the open chromatin www.biorxiv.org/content/10.1...
▶️RoboATAC - automated ATAC-seq
▶️Deep learning models: motif orientation, spacing, flanking bases
▶️Nucleosome positioning analysis
Transcription factors create accessibility through distinct mechanisms involving nucleosome sliding and eviction. A) Estimation of nucleosome-free (NFR) and nucleosomal fragment probabilities using ATAC-seq fragment size distributions. B) Example genomic locus showing ATAC insertion profile, nucleosome occupancy scores, and dyad positions inferred from NucleoATAC.
July 27, 2025 at 12:31 PM
teiflab.bsky.social
Wang et al, 2025. Genome-Wide Investigation of Transcription Factor Occupancy and Dynamics Using cFOOT-seq www.biorxiv.org/content/10.1...
cFOOT-seq maps chromatin accessibility, nucleosome occupancy, and TF footprints A. Schematic of the cFOOT-seq workflow. After cell permeabilization, dsDNA deaminases (blue) convert cytosine to uracil in accessible chromatin DNA (blue lines), but DNA occupied by nucleosomes or transcription factors (TFs) (gray lines) remains unconverted. The profile of DNA conversion rate defines nucleosome occupancy and TF footprints.
July 22, 2025 at 8:55 AM
teiflab.bsky.social
This graph shows no correlation woth GBP/USD
July 10, 2025 at 10:57 AM
teiflab.bsky.social
May 25, 2025 at 1:23 PM
teiflab.bsky.social
Native nucleosomes intrinsically encode genome organization principles www.nature.com/articles/s41...
▶️Condensed purified native mononucleosomes with polyamines
▶️Nucleosomes from A compartments have low condensability and those from B compartments have high condensability
May 10, 2025 at 7:42 PM
teiflab.bsky.social
Kable et al., 2025. Compromised 2-start zigzag chromatin folding in immature mouse retina cells driven by irregularly spaced nucleosomes with short DNA linkers www.biorxiv.org/content/10.1...
▶️In mature retina cells, the fraction of short-linker nucleosomes is lower -> stronger chromatin compaction.
The formation of condensed heterochromatin is critical for establishing cell-specific transcriptional programs. To reveal structural transitions underlying heterochromatin formation in maturing mouse rod photoreceptors, we apply cryo-EM tomography, AI-assisted deep denoising, and molecular modeling. We find that chromatin isolated from immature retina cells contains many closely apposed nucleosomes with extremely short or absent nucleosome linkers, which are inconsistent with the typical two-start zigzag chromatin folding. In mature retina cells, the fraction of short-linker nucleosomes is much lower, supporting stronger chromatin compaction. By Cryo-EM-assisted nucleosome interaction capture we observe that chromatin in immature retina is enriched with i±1 interactions while chromatin in mature retina contains predominantly i±2 interactions typical of the two-start zigzag. By mesoscale modeling and computational simulation, we clarify that the unusually short linkers typical of immature retina are sufficient to inhibit the two-start zigzag and chromatin compaction by the interference of very short linkers with linker DNA stems. We propose that this short linker composition renders nucleosome arrays more open in immature retina and that, as the linker DNA length increases in mature retina, chromatin fibers become globally condensed via tight zigzag folding. This mechanism may be broadly utilized to introduce higher chromatin folding entropy for epigenomic plasticity.
May 5, 2025 at 12:52 PM
teiflab.bsky.social
Ultrastable and versatile multimeric ensembles of FoxP3 on microsatellites www.cell.com/molecular-ce...
▶️FoxP3 recognizes a variety of TnG repeat microsatellites
▶️FoxP3 multimers are ultrastable, can bridge 2–4 DNA duplexes
▶️Nucleosomes can facilitate FoxP3 assembly by inducing local DNA bending
Microsatellites are essential genomic components increasingly linked to transcriptional regulation. FoxP3, a transcription factor critical for regulatory T cell (Treg) development, recognizes TTTG repeat microsatellites by forming multimers along DNA. However, FoxP3 also binds a broader range of TnG repeats (n = 2–5), often at the edges of accessible chromatin regions. This raises questions about how FoxP3 adapts to sequence variability and the potential role of nucleosomes. Using cryoelectron microscopy and single-molecule analyses, we show that murine FoxP3 assembles into various distinct supramolecular structures, depending on DNA sequence. This structural plasticity enables FoxP3 to bridge 2–4 DNA duplexes, forming ultrastable structures that coordinate multiple genomic loci. Nucleosomes further facilitate FoxP3 assembly by inducing local DNA bending, creating a nucleus that recruits distal DNA elements through multiway bridging. Our findings thus reveal FoxP3’s unusual ability to shapeshift to accommodate evolutionarily dynamic microsatellites and its potential to reinforce chromatin boundaries and three-dimensional genomic architecture.
April 5, 2025 at 9:54 PM