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teiflab.bsky.social
Teif lab
@teiflab.bsky.social
2.9K followers 1K following 320 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
Congratulations to Negin Behboodi on successfully passing your PhD viva! We are so proud of you! Keep an eye out for Negin's upcoming big papers! And thank you to the kind examiners @mspivakov.bsky.social and @amarcobio.bsky.social!
January 14, 2026 at 6:42 PM
teiflab.bsky.social
Schaepe et al, 2026. Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells www.cell.com/cell/fulltex...
The molecular details governing transcription factor (TF) binding and the formation of accessible chromatin are not yet quantitatively understood—including how sequence context modulates affinity, how TFs search DNA, the kinetics of TF occupancy, and how motif grammars coordinate binding. To resolve these questions for a human TF, erythroid Krüppel-like factor (eKLF/KLF1), we quantitatively compare, in high throughput, in vitro TF binding rates and affinities with in vivo single-molecule TF and nucleosome occupancies and in vivo-derived deep learning models. We find that 40-fold flanking sequence effects on affinity are consistent with distal flanks tuning TF search parameters and captured by a linear energy model. Motif recognition probability, rather than time in the bound state, drives affinity changes, and in vitro and in nuclei measurements exhibit consistent, minutes-long TF residence times. Finally, in vitro biophysical parameters predict in vivo sequence preferences and single-molecule chromatin states for unseen motif grammars.
January 11, 2026 at 11:37 PM
teiflab.bsky.social
Structural organization and function of telomeric chromatin [Review by Ruben van der Lugt & Jacqueline Jacobs] www.nature.com/articles/s41...
Fig. 1: Schematic of the human telomeric chromatin architecture. The human telomere is made up of TTAGGG repeats arranged into nucleosomes, bound by a six-subunit shelterin complex (comprising TRF1, TRF2, RAP1, TIN2, TPP1 and POT1). Some complexes are depicted without TPP1 and POT1, which it has been suggested are less abundant than the other subunits. Recent in vitro structural analyses of telomeric chromatin revealed a columnar stacking of histones on TTAGGG repeats, characterized by face-to-face nucleosome arrangements, as well as an alternative open configuration where two histone octamers are oriented at a nearly 90° angle. These in vitro columnar arrays exhibit an NRL of approximately 130 bp. In vivo, however, the telomeric NRL is 157 bp, longer than the NRL of the proposed columnar histone arrangement, but shorter than the ~197-bp NRL of bulk chromatin. To reconcile this, we depict here a model in which shelterin remodels the telomeric chromatin to integrate features of a columnar nucleosome organization with the nucleosome periodicity observed in vivo. At the telomere terminus, a 3′ single-stranded overhang of TTAGGG repeats invades the duplex telomeric DNA to form a lariat structure known as the T-loop. This loop structure serves a protective function by preventing the telomere from being recognized as damaged DNA. The size of the T-loop is variable and may differ between telomeres, contributing to the structural heterogeneity of the telomere. The extent to which nucleosomes are present within the T-loop remains unclear. Fig. 2: Impact of the TPE on the local and distal chromatin environment. Telomere elongation results in the repression of genes in the vicinity of telomeres, a phenomenon known as the TPE. a, Schematic of the repression of telomere-proximal genes via the classical TPE that has been shown at telomere-adjacent artificial reporter genes in human cells. Upon elongation, telomeres accumulate repressive histone modifications (indicated in red) through the activity of a histone methyltransferase (HMT) and HP1. The repressive heterochromatin environment of elongated telomeres spreads to nearby subtelomeric genes (indicated with red and orange DNA strands), resulting in transcriptional repression. The strength of silencing diminishes as the distance from the telomere increases (indicated with fading arrows). Conversely, upon telomere shortening, the human TPE (at telomere-adjacent transgenes) is characterized by loss of the repressive histone modification H3K9me3 and gain of the activating modification H3K9ac. In contrast to telomere-adjacent artificial reporter genes, at natural subtelomeres, spreading of repressive histone modifications from telomeres is not consistently observed, probably due to the presence of boundary elements. b, Schematic of telomere-mediated repression of telomere-distal genes via TPE-OLD. Elongated telomeres acquire the ability to form long-distance loops between telomeres and interstitial telomere sequences (ITSs; that is, sequences of TTAGGG repeats outside of the telomeres). Looping requires binding of shelterin to an ITS and results in transcriptional repression of the affected gene. Fig. 3: Heterogeneity of (sub)telomeric chromatin and its reorganization upon telomere elongation. a, Telomeric and subtelomeric chromatin are organized into distinct domains. The subtelomeric TAR1 site acts as a TSS for the telomeric non-coding RNA TERRA (depicted in red for UUAGGG and in orange for subtelomere-derived RNA). The canonical TERRA promoter contains a high density of CpG dinucleotides, regulated by the DNA methyltransferases DNMT1 and DNMT3B. In contrast, certain subtelomeres (variable across cell lines) contain non-canonical TERRA promoters that lack CpG-rich regions and escape regulation by DNA methylation. Binding of CTCF and cohesin to the centromeric side of TAR1 maintains transcriptionally competent chromatin at the TSS and facilitates the recruitment of RNA polymerase II. The telomeric tract itself displays a bivalent pattern of histone modifications, with both activating (H3K4me3 and H3K27ac) and repressive marks (H3K9me3, H3K27me3 and H4K20me3). TERRA modulates this environment through the formation of RNA:DNA hybrids (R-loops) and G4s. Furthermore, RNA- or G4-binding chromatin remodellers, including Suv39H1, ORC1, NoRC, PRC2 and FUS, are recruited by TERRA and alter the epigenetic landscape. G4-binding proteins, including CTCF and YY1, mediate long-range interactions between distal G4s, contributing to higher-order chromatin organization. The telomeric shelterin complex itself is heterogeneous and probably assembles into subcomplexes (for example, TRF1–TIN2–TPP1–POT1 or TRF2–RAP1). TRF2 is essential for formation of the terminal T-loop, which requires direct interaction between TRF2 and nucleosomes. TRF2-mediated stabilization of nucleosomes may prevent branch migration at the base of the loop, which would result in cleavage of the loop by resolvases. b, TERT-mediated elongation alters the chromatin of telomeres. The length of TERRA molecules is proportional to the telomere length, allowing increased recruitment of chromatin-modifying enzymes… Fig. 4: Schematic of the ALT pathway. ALT is a telomerase-independent, cancer-specific mechanism of telomere maintenance enabled by alterations to the telomeric chromatin. Between 10 and 15% of cancers activate the ALT pathway to maintain telomere length in a telomerase-independent manner. ALT+ cancers frequently display loss of ATRX–DAXX histone chaperone activity, resulting in reduced deposition of the histone variant H3.3 at telomeres and, consequentially, progressive decompaction of the telomeres. This chromatin disruption promotes increased TERRA transcription, leading to accumulation of R-loops and G4s. ALT+ telomeres also display increased levels of the repressive histone mark H3K9me3, partially due to additional mutations such as those encoding the G34R substitution in H3.3 and the R132H substitution in IDH1, which inhibit the histone demethylase KDM4B. The combined effect of R-loops, G4s and decreased nucleosome occupancy cause persistent replication stress, ultimately giving rise to telomeric breaks. Broken telomeres are further enriched in H3K9me3 due to the break-induced recruitment of the CHAMP1–POGZ–HP1 complex. These telomeric breaks are clustered in APBs, membrane-less condensates formed through HP1- and PML-dependent phase separation. Within APBs, broken telomeres invade homologous telomeric templates to initiate HDR-mediated extension. Invasion of the broken strand is stimulated by RAD51AP1, which promotes the switch from TERRA R-loops to stable telomeric D-loops, where telomere elongation takes place.
January 7, 2026 at 8:41 PM
teiflab.bsky.social
The famous "It takes two to think" by @itaiyanai.bsky.social and martinlercher.bsky.social (www.nature.com/articles/s41...) may have some ramifications in the era of AI :)
Four-panel black-and-white stick-figure cartoon comparing work styles. Panel 1, “Boss”: one person sits on a cart full of books and points forward while three others pull the cart. Panel 2, “Leader”: four people pull the cart together, with the front person pointing the direction while still pulling. Panel 3, “Introvert”: a single person pulls the cart alone. Panel 4, “Introvert with AI”: the same person walks easily while a small robot pulls two book-filled carts behind them.
January 4, 2026 at 3:27 PM
teiflab.bsky.social
Wishing you a happy, healthy, successful and science-filled new year!
December 31, 2025 at 2:04 PM
teiflab.bsky.social
Rudnizky et al., 2025. Ultrafast CTCF dynamics control cohesin barrier function www.biorxiv.org/content/10.1...
December 4, 2025 at 6:50 PM
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