Study Finds Wnt/β-catenin Signaling Can Actively Reshape Chromatin, Not Just Activate Pre-set States
Researchers using time-resolved ATAC-seq and CUT&RUN analyses in HEK293T cells have found that β-catenin, a key Wnt signaling protein, can act as a pioneer-like factor to open previously inaccessible chromatin regions and establish new regulatory elements. This challenges the prevailing view that Wnt/β-catenin signaling merely activates pre-existing, preprogrammed regulatory states. The finding has implications for understanding how Wnt signaling drives context-dependent gene regulation in development and disease.
A new preprint study on bioRxiv reports that Wnt/β-catenin signaling does more than switch on pre-existing gene regulatory programs — it can actively remodel chromatin to create new ones. Using time-resolved ATAC-seq and CUT&RUN in HEK293T cells, researchers identified two distinct classes of Wnt-responsive elements (WREs): conventional WREs that are constitutively accessible and pre-bound by TCF/LEF transcription factors, and a newly described class of 'latent enhancers' that are initially closed but become accessible following Wnt pathway activation. At these latent enhancers, β-catenin works together with HDAC1 and CBP to remodel chromatin and enable TCF/LEF binding, functioning in a pioneer-like capacity. This positions β-catenin not just as a transcriptional co-activator but as a central regulator of both transcriptional control and chromatin remodeling. The results provide a mechanistic framework for the dynamic, context-dependent nature of Wnt-driven transcription, which may help explain how the same signaling pathway produces different outcomes in different cell types or disease states.
What's missing
As a preprint, this study has not yet undergone peer review, so its findings should be interpreted with caution. The experiments were conducted exclusively in HEK293T cells (a human embryonic kidney cell line), and it remains unclear whether the same pioneer-like β-catenin activity occurs in primary cells, other cell types, or in vivo developmental contexts. The precise mechanistic relationship between HDAC1 (typically associated with transcriptional repression) and CBP (a co-activator) at these sites warrants further investigation.
What different sources said
- bioRxivCenter
Enhancer pioneering activity of Wnt/β-catenin signaling
Related
Gut Bacteria Enzyme Found to Break Down Heat-Processed Food Compounds, Producing Novel Biogenic Amines
Researchers have discovered that an enzyme in common gut bacteria can degrade N-epsilon-carboxymethyllysine (CML), a compound formed during thermal food processing, producing previously unknown biogenic amines. The enzyme, ornithine decarboxylase SpeC from enterobacteria, acts on CML and related modified lysine derivatives through a low-level 'underground' catalytic activity. This finding suggests a previously unrecognized communication axis between thermally processed dietary compounds and gut microbial physiology, with potential implications for host health.
Full-Length Gene Sequencing Reveals Two Distinct Bacterial Communities in Black-Legged Ticks Expanding Into Canada
Researchers used Oxford Nanopore full-length 16S rRNA gene sequencing to characterize the microbiome of Ixodes scapularis black-legged ticks collected in Nova Scotia, Canada, distinguishing between tick-adapted bacteria and environmentally acquired bacteria. The study comes as I. scapularis — the primary vector of Lyme disease — is rapidly expanding northward into Canada due to climate change. The findings suggest that environmentally derived bacteria in tick microbiomes are not mere contamination, which has implications for how tick microbiome data is collected and interpreted across surveillance studies.
Study Identifies Metabolic Link Between Cell Envelope Stress and Biofilm Formation in Bacteria
Researchers have discovered that the metabolite acetyl-CoA directly inhibits enzymes that degrade the bacterial signaling molecule c-di-GMP, connecting cell envelope biosynthesis stress to biofilm formation in Pseudomonas aeruginosa. The study found that sub-inhibitory concentrations of antibiotics targeting early peptidoglycan biosynthesis — but not other antibiotic classes — elevate c-di-GMP levels by reducing phosphodiesterase activity, with acetyl-CoA competing for the enzyme active site. Because the relevant enzyme domain is broadly conserved across bacterial species, this checkpoint mechanism may be widespread and could have implications for understanding antibiotic-induced biofilm responses.