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teiflab.bsky.social
Teif lab
@teiflab.bsky.social
3.1K followers 1.1K following 390 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
AlBawardi et al, 2026. Irregular nucleosome positioning governs a crystalline to liquid-like phase transition and tunes chromatin accessibility www.biorxiv.org/content/10.6...
▶️heterochromatin-like sequences produce compact fibres
▶️positional irregularity (>2-3 bp) triggers a state transition
Abstract: Chromatin must fold tightly enough to protect the genome while being sufficiently accessible for DNA dependent processes such as transcription. The physical rules that balance these competing roles remain unclear, as DNA sequence encodes both biochemical information such as transcription factor binding sites, and biophysical cues that shape chromatin structure. Here, using synthetic chromatin fibres assembled from physiologically relevant DNA sequences, we show that nucleosome positioning dictates the material state of chromatin. Heterochromatin-like sequences produce compact fibres stabilised by nucleosome stacking, whereas euchromatin-like sequences generate irregular nucleosome positioning that yields disrupted, heterogeneous, and mechanically deformable fibres. Quantitative polymer modelling reveals that these irregular arrays are highly dynamic, continually sampling a broad ensemble of conformations as nucleosome stacking breaks down. We identify two previously unrecognised thresholds encoded by nucleosome positioning: minimal positional irregularity (2–3 bp) triggers a transition from an ordered paracrystalline state to a liquid-like phase, whereas an order of magnitude greater irregularity (∼18 bp) is required to generate accessibility and mechanical fragility permissive for transcription factor binding. Euchromatin-like arrays reside at this accessibility threshold. These findings indicate that nucleosome positioning tunes chromatin toward or away from critical structural states that couple genome protection, chromatin dynamics, and transcriptional potential—providing a physical mechanism that helps connect DNA sequence to gene expression.
August 30, 2026 at 10:52 AM
teiflab.bsky.social
Luo et al, 2026 (review). The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options link.springer.com/article/10.1...
🤯548 references!
August 18, 2026 at 8:09 PM
teiflab.bsky.social
Woolfe et al, 2026. Decoding the mystery of ultra-conservation in developmental enhancers: a role for nucleosome positioning, DNA structure and transcription factor binding www.biorxiv.org/content/10.6...
▶️conserved non-coding elements ... favor nucleosome occupancy at their borders
July 26, 2026 at 9:34 AM
teiflab.bsky.social
Finally: nucleosome positioning as highlighting with a marker in a book. Just as highlighted words or sentences stand out differently, where nucleosomes sit can make parts of the genome easier or harder to read. This analogy took me a while to come up with! 4/4
July 10, 2026 at 8:02 PM
teiflab.bsky.social
Next: DNA methylation as accents on letters. In languages like French, an accent can change how a letter or word is read; methylation marks can change how cells read DNA, without changing the underlying sequence. Has anyone seen this analogy used before? 3/4
July 10, 2026 at 8:02 PM
teiflab.bsky.social
First: the genome as a book. DNA sequence is the text, written with four letters - A, T, G and C. This is a standard analogy, but it gives students a clear starting point before introducing gene regulation. 2/4
July 10, 2026 at 8:02 PM
teiflab.bsky.social
Chen et al 2026. Genome-wide rotational and translational phasing of nucleosomes with human transcription factors www.cell.com/molecular-ce...
▶️ In vivo nucleosome phasing measured on the same TF-bound DNA molecule
▶️ Phasing around CTCF sites is DNA encoded
▶️ FoxA and NFIA phase adjacent nucleosomes
How transcription factors (TFs) and their binding sites organize and engage nucleosomes at natural genomic locations remains poorly understood. Here, we develop Benzonase-seq to measure the rotational phasing of nucleosomes in human cells and enhance chromatin immunoprecipitation (ChIP)-exo (v6) to measure rotational phasing on the same DNA molecule bound by a TF. Unbound CTCF sites were found to be rotationally accessible on nucleosomes, and this rotational accessibility is encoded by classical dinucleotide periodicities. CTCF binding results in nucleosome displacement to adjacent DNA phasing sequences. Upon examining 40 TF classes, unbound sites were found to be phased either inward or outward or to lack phasing. In all examined cases, TF binding (e.g., NFIA and FoxA) results in adjacent rotational and translational phasing, which is not dinucleotide encoded. Benzonase-seq also more robustly maps nucleosome and subnucleosome positions in hard-to-map CpG islands. These findings provide a clearer view of how TFs engage and position nucleosomes to shape the natural chromatin landscape.
July 7, 2026 at 8:58 AM
teiflab.bsky.social
Great preprint by @vram142.bsky.social & Co www.biorxiv.org/content/10.6... "fiber homotypy," where chromatin fibers with similar nucleosome spacing interact more frequently in 3D

--> Related to our previous "nucleosome homology recognition" in chromatin royalsocietypublishing.org/rsif/article...
June 12, 2026 at 4:51 PM
teiflab.bsky.social
Come celebrate Professor Leo Schalkwyk with us!

We’re holding a one-day symposium to mark Leo's remarkable career and many contributions to genomics.
📆26 June 2026
📍University of Essex, Colchester
Details and registration: schalkwykfest.essex.ac.uk
There will be a BBQ as well!
June 10, 2026 at 8:58 PM
teiflab.bsky.social
Sun et al, 2026. NuRD-enabled CTCF-TET crosstalk orchestrates epigenome reprogramming and genome architecture www.cell.com/molecular-ce...
June 4, 2026 at 11:50 AM
teiflab.bsky.social
The +1 nucleosome functions in Pol II transcription initiation and the transition to elongation www.biorxiv.org/content/10.6... [Yumeng Zhan, Julio Abril-Garrido, Frauke Grabbe, Paulina Seweryn, Ute Neef, Christian Dienemann, Patrick Cramer]
May 15, 2026 at 10:59 AM
teiflab.bsky.social
Very interesting analogy to micelle! Reminded me visually about this model www.cell.com/biophysj/ful...
May 3, 2026 at 10:06 AM
teiflab.bsky.social
Adhireksan et al, 2026. Linker histones consolidate heterogenous nucleosome fiber contacts by linking together multiple nucleosomes www.nature.com/articles/s41...
The consensus mode for linker histone (H1) association coincides with ‘on-dyad’ binding to an individual nucleosome, making it challenging to rationalize the chromatin dynamics and compacting activities of H1 in the context of a highly heterogeneous structural scaffold. Here, we investigate the activity of the somatic H1 variants by conducting crystallographic analysis of nucleosomal assemblies and characterization of nucleosome array condensates, which recapitulate long-range nucleosome fiber interactions in chromatin. H1 is observed to associate variant-dependently with nucleosomes through a diversity of binding modes that include linking multiple nucleosomes/fibers together. Binding versatility is facilitated by the proclivity of the H1 globular domain to recognize DNA structural motifs, which are similar between an individual nucleosome and specific niches within clusters of nucleosomes. We propose that linker histones support a structurally and functionally complex repertoire for chromatin regulation by assuming a variety of context-and variant-dependent DNA binding modes.
March 9, 2026 at 10:30 AM
teiflab.bsky.social
Nucleosome aficionados! Our new review "Nucleosome spacing across cell types, diseases, and ages" is out in NAR: academic.oup.com/nar/article/...

A huge effort to pull together what we’ve learned about nucleosome spacing in many systems. Enjoy!
@milena-bikova.bsky.social @chrsclrksn.bsky.social
Figure 1.(A) Classical gel electrophoresis experiments showing mono-, di-, tri-, tetra-, and further multinucleosome bands upon chromatin digestion. (B) The nucleosome repeat length (NRL) is defined as the genomic distance between the centres of two neighbouring nucleosomes. Figure 2.Nucleosome mapping using MNase-seq versus ATAC-seq. (A) In MNase-seq, nucleosomes in both open and tightly packed genomic regions are accessible to digestion. MNase preferentially cleaves DNA between nucleosomes and digests DNA until it encounters a histone octamer, which provides a footprint of nucleosome-protected DNA regions. (B) Bulk MNase-seq results in averaged maps across millions of cells, effectively capturing all possible nucleosome positioning configurations. (C) Single-cell MNase-seq (scMNase-seq) results in a noisier and sparser signal. The resulting footprints still represent nucleosome-protected regions, but not all nucleosomes are represented. (D) In ATAC-seq, open regions can be accessed by the enzyme Tn5 transposase, which can insert primers in regions free from the binding of nucleosomes and transcription factors (TFs). (E) For open chromatin regions, nucleosome maps can be obtained from ATAC-seq similar to MNase-seq. (F) Closed, tightly packed chromatin regions may be less represented in ATAC-seq nucleosome maps. Figure 5.Molecular mechanisms affecting nucleosome spacing. (A) Linker histones H1 and nonhistone chromatin proteins which compete with H1s and modulate nucleosome spacing through structural and electrostatic mechanisms. (B) Chromatin remodellers actively reposition nucleosomes following context-dependent rules. (C) Cell state-dependent chromatin boundaries formed by CTCF and other structural proteins, as well as associated recruitment of chromatin remodellers which space nucleosomes. (D) Gene activity associated with remodeller action and RNA polymerases transcribing through the nucleosomes, leading to smaller distances between nucleosomes in regulatory regions and gene bodies. (E) DNA sequence repeats of different types. Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).
March 5, 2026 at 9:32 PM
teiflab.bsky.social
February 11, 2026 at 12:18 PM
teiflab.bsky.social
I found another paper where whole-chromosomes have been coloured in lymphocytes journals.plos.org/plosone/arti... Here the positions of chromosomes 9 and 22 are not far but not convincingly close. It would be cool to find a figure with territories of all chromosomes coloured as in the one above
February 8, 2026 at 4:57 PM
teiflab.bsky.social
Probably this one can work haematologica.org/article/view...
February 8, 2026 at 12:58 PM
teiflab.bsky.social
The closest image I found is this relative spatial positioning of chromosomes between GM12878 and K562 cell lines link.springer.com/article/10.1.... But I am looking for a more direct visualisation in the style of chromosome territories, and ideally not in cancer cells
February 8, 2026 at 12:35 PM
teiflab.bsky.social
Preparing a lecture about cancer genomics. Looking for a 3D map of human chromatin to show chromosomes 22 and 9 close to each other to demonstrate Philadelphia chromosome translocation. Chromosome territories like the one below don't show them together. Any other visualisations in this style?
February 8, 2026 at 12:23 PM
teiflab.bsky.social
Today we had very nice interactions in the University of North Dakota (remotely)! Thank you very much @adhasarathy.bsky.social, Motoki Takaku & Co for the invitation to give this talk and hosting the visit!
January 21, 2026 at 11:42 PM
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