Biology subjects

Krueger, C.

Publications and source records attributed to Krueger, C..

18 recordsLinked to original sources

bioRxiv2026

Pathogen cell wall degrading enzymes facilitate extracellular vesicles to deliver RNA into plants

Extracellular vesicles (EVs) can deliver RNA and proteins into host cells to manipulate immunity; but how EVs transverse the cell wall is unknown. Using the fungal pathogen Botrytis cinerea that induces cross-kingdom RNA interference in plants, we uncovered that EV-mediated RNA delivery was dependent on cell wall degrading enzymes. Through fluorescence and transmission electron microscopy, and molecular genetic techniques, we demonstrate that EV-associated proteins compromise the plant cell wall, thereby facilitating RNA delivery. Notably, cell wall degrading enzymes are commonly associated with EVs across plant-colonizing bacterial, fungal and oomycete species, indicating a conserved role in EV transport across cell walls. These findings uncover a formerly unknown mechanism by which cell wall degrading enzymes facilitate EVs to transverse the cell wall for cargo delivery in cross-kingdom communication.

plant biology↗

bioRxiv2025

Sex- and age-differences in cellular hallmarks of aging in a species with female-biased longevity and environmental sex determination

Cellular hallmarks of aging have been discovered and characterized in a number of model species for studying aging biology - such as humans, mice, fruit flies, and nematodes. Whether these canonical age-related changes to cellular physiology are present across diverse species that have variable rates of demographic aging remains less studied. Here, we tested whether several ubiquitous cellular hallmarks of aging - mitochondrial function, reactive oxygen species generation, and inducible DNA damage - change with age and in a sex-dependent manner in a species with indeterminate growth and reproduction (painted turtles, Chrysemys picta). A further feature of their biology that recommends them for an ecological model of vertebrate aging is their female-biased longevity, despite an absence of genotypic sex determination. Thus lifespan and aging may be reliable features of sex-specific life-histories. We measured aspects of mitochondrial health (cellular basal, maximal, and spare oxygen consumption rates), cellular levels of reactive oxygen species, and aspects of DNA damage and repair from exposure to UVB. We used these measures across several physiological axes as proxies for age-related physiological dysfunction. We further assessed our measures across several populations of painted turtles. We found that sex explained the largest proportion of variation, with males differing from females in mitochondrial function, reactive oxygen species production, and inducible DNA damage. In several cases, age significantly interacted with sex, but the effect size was small relative to sex alone. Thus, we found that sex, rather than age or size, was a consistent predictor of cellular aging physiological in this species with where females live longer and age slower.

physiology↗

bioRxiv2025

Murine Toll-like receptor 8 is a nucleic acid multi-sensor detecting 2',3'-cyclic monophosphate guanosine as well as combinations of ribo-, deoxy-, cyclic nucleotides, and nucleosides

Toll-like receptor 8 (TLR8) in humans senses RNA degradation products and elicits an inflammatory immune response. In contrast, the ligand specificity and function of its murine counterpart mTLR8, long considered non-functional, remain poorly defined. Here, we established an agonist combination model of poly-deoxythymidine (poly-dT) DNA and TLR7/8 binding site 1 agonists such as uridine or the benzazepine compound TL8-506, which activates mTLR8, while suppressing mTLR7 signaling. Extensive agonist analysis based on this model revealed that 2,3-cyclic guanosine monophosphate (2,3-cGMP) serves as a natural ligand for mTLR8, suggesting functionality of its binding site 1 without engagement of site 2. In addition, 2,3-cyclic uridine monophosphate, bacterial single-stranded (ss) DNA, double-stranded (ds) DNA fragments, microRNAs, ssRNA derived from HIV1, SARS-CoV-2, or bacterial sources all potentiate mTLR8 sensing of site 1 agonists. All these stimuli induce distinct inflammatory responses from murine macrophages and microglia via TLR8. In vivo, intrathecal administration of TL8-506 and poly-dT led to microglial accumulation and neuronal injury in the murine cerebral cortex through TLR8, highlighting the potential neuropathological consequences of mTLR8 activation. Taken together, our study defines mTLR8 as a nucleic acid sensor detecting 2,3-cGMP as well as combinations of ssDNA, dsDNA, ssRNA fragments, 2,3-cyclic nucleotide monophosphates, and nucleosides, with implications for host defense and neuroinflammation.

immunology↗

bioRxiv2024

A lymphoid tissue chemokine checkpoint prevents loss of CD8+ T cell functionality

The generation of effector CD8+ T cells (TEFF) requires activation of naive CD8+ T cells (TN) by dendritic cells (DCs) within lymphoid tissue. To date, it remains elusive how the duration of TN-DC interactions and integration of activation signals are controlled in vivo. Here, we report that lymphoid stroma-secreted ligands for CCR7 constrained interaction duration by gradually inducing CD8+ T cell release from DCs. At late time points of interactions, CCR7 ligands repositioned the F-actin-promoting factor DOCK2 away from the DC interface to enable CD8+ T cell detachment, proliferation onset and acquisition of cytotoxicity. Lack of CCR7 signaling, as during ex vivo activation or in chronically inflamed lymphoid tissue, caused sustained T cell-DC interactions, and generated dysfunctional TEFF with high expression of inhibitory receptors, impaired antimicrobial activity, and poor recall responses. In sum, our findings uncover that lymphoid stromal chemokines act as built-in "disruptors" of T cell-DC interactions for long-term preservation of TEFF functionality.

immunology↗

bioRxiv2023

Maternal SMARCA5 is required for major ZGA in mouse embryos

Zygotic genome activation (ZGA) in mice takes place in two waves, a minor wave in the one-cell embryo, and a major wave at the two-cell stage, both accompanied by global transcriptional and epigenetic reprogramming. However, the orchestration of these reprogramming events by maternal factors deposited in the oocyte is not yet entirely understood. We and others have recently shown that epigenetic modifiers such as SMARCA5 (the main ATPase in ISWI complexes) can initiate the ZGA transcriptional programme in vitro. So far, the role of SMARCA5 in ZGA in vivo has not been addressed, as constitutive knock-out mice lacking SMARCA5 are not viable. We have overcome this limitation by using the targeted protein-depletion system Trim Away to degrade SMARCA5 in early zygotes. We further harnessed the power of single cell multi-omics (scNMT-seq) and showed that in the absence of SMARCA5, major ZGA genes fail to be upregulated at the two-cell stage. This is explained by the lower accessibility and disrupted nucleosome positioning at their promoters and distal regulatory regions, compared to wild-type embryos. In contrast, we show that global chromatin accessibility at the two-cell stage is higher in SMARCA5 depleted embryos compared to control embryos, and this is accompanied by other global structural changes involving heterochromatic regions. Our results show that SMARCA5 has a global regulatory role at the two-cell stage, which includes the control of ZGA gene promoters and distal regulatory regions.

developmental biology↗

bioRxiv2023

Dynamic DNA methylation turnover at the exit of pluripotency epigenetically primes gene regulatory elements for hematopoietic lineage specification

Epigenetic mechanisms govern developmental cell fate decisions, but how DNA methylation coordinates with chromatin structure and three-dimensional DNA folding to enact cell-type specific gene expression programmes remains poorly understood. Here, we use mouse embryonic stem and epiblast-like cells deficient for 5-methyl cytosine or its oxidative derivatives (5-hydroxy-, 5-formyl- and 5-carboxy-cytosine) to dissect the gene regulatory mechanisms that control cell lineage specification at the exit of pluripotency. Genetic ablation of either DNA methyltransferase (Dnmt) or Ten-eleven-translocation (Tet) activity yielded largely distinct sets of dysregulated genes, revealing divergent transcriptional defects upon perturbation of individual branches of the DNA cytosine methylation cycle. Unexpectedly, we found that disrupting DNA methylation or oxidation interferes with key enhancer features, including chromatin accessibility, enhancer-characteristic histone modifications, and long-range chromatin interactions with putative target genes. In addition to affecting transcription of select genes in pluripotent stem cells, we observe impaired enhancer priming, including a loss of three-dimensional interactions, at regulatory elements associated with key lineage-specifying genes that are required later in development, as we demonstrate for the key hematopoietic genes Klf1 and Lyl1. Consistently, we observe impaired transcriptional activation of blood genes during embryoid body differentiation of knockout cells. Our findings identify a novel role for the dynamic turnover of DNA methylation at the exit of pluripotency to establish and maintain chromatin states that epigenetically prime enhancers for later activation during developmental cell diversification. HighlightsO_LIWe perform a detailed epigenetic characterisation of the mouse embryonic stem cell (ESC) to epiblast-like cell (EpiLC) transition in wild type, Tet triple-knockout (TKO) and Dnmt TKO lines and develop a novel clustering approach to interrogate the data. C_LIO_LITet TKO reduces H3K4me1 and H3K27ac levels across enhancer elements upon pluripotency exit whilst Dnmt TKO affects only H3K4me1 levels, suggesting a novel role for oxidative derivatives in H3K4me1 deposition. C_LIO_LITet TKO and Dnmt TKO affect enhancer priming in EpiLCs which is associated with failure to upregulate hematopoietic genes upon differentiation. C_LIO_LILong-range chromosomal interactions between primed enhancers and their target genes are weakened in both Dnmt and Tet TKO. C_LI

molecular biology↗

bioRxiv2022

NANOGP1, a tandem duplicate of NANOG, exhibits partial functional conservation in human naive pluripotent stem cells

Gene duplication events are important drivers of evolution by providing genetic material for new gene functions. They also create opportunities for diverse developmental strategies to emerge between species. To study the contribution of duplicated genes to human early development, we examined the evolution and function of NANOGP1, a tandem duplicate of the key transcription factor NANOG. We found that NANOGP1 and NANOG have overlapping but distinct expression profiles, with high NANOGP1 expression restricted to early epiblast cells and naive-state pluripotent stem cells. Sequence analysis and epitope-tagging of the endogenous locus revealed that NANOGP1 is protein-coding with an intact homeobox domain. NANOGP1 has been retained only in great apes, whereas Old World monkeys have disabled the gene in different ways including point mutations in the homeodomain. NANOGP1 is a strong inducer of naive pluripotency; however, unlike NANOG, it is not required to maintain the undifferentiated status of human naive pluripotent cells. By retaining expression, sequence and partial functional conservation with its ancestral copy, NANOGP1 exemplifies how gene duplication and subfunctionalisation can contribute to transcription factor activity in human pluripotency and development. Summary statementEstablishing that NANOGP1 has retained partial functional conservation with its ancestral copy NANOG sheds light on the role of gene duplication and subfunctionalisation in human pluripotency and development.

developmental biology↗

bioRxiv2021

The distinct effects of MEK and GSK3 inhibition upon the methylome and transcriptome of mouse embryonic stem cells

Mouse embryonic stem cells (mESCs) were first cultured in vitro in serum-containing medium with leukaemia inhibitory factor, in which they exhibit heterogeneous expression of both pluripotency and some early differentiation markers. Over the last decade, however, it has become commonplace to grow mESCs with inhibitors of MEK and GSK3 signalling, which together elicit a more homogeneously naive state of pluripotency. Whilst 2i/L-cultured mESCs have been shown to be globally hypomethylated, a comprehensive understanding of the distinct effects of these signalling inhibitors upon the DNA methylome is still lacking. Here we carried out whole genome bisulphite and RNA sequencing of mESCs grown with MEK or GSK3 inhibition alone, including different time points and concentrations of MEK inhibitor treatment. This demonstrated that MEK inhibition causes a dose-dependent impairment of maintenance methylation via loss of UHRF1 protein, as well as rapid impairment of de novo methylation. In contrast, GSK3 inhibition triggers impairment of de novo methylation alone, and consequent hypomethylation is enriched at enhancers with a 2i/L-specific chromatin signature and coincides with upregulation of nearby genes. Our study provides detailed insights into the epigenetic and transcriptional impacts of inhibiting MEK or GSK3 signalling in mouse pluripotent cells. HighlightsO_LIMEK inhibition causes dose-dependent impairment of maintenance methylation via loss of UHRF1 protein, as well as impairment of de novo methylation. C_LIO_LIGSK3 inhibition triggers impairment of de novo methylation alone, which results in hypomethylation of enhancers and non-CGI promoters. C_LIO_LIEnhancers that are hypomethylated following GSK3 inhibition are enriched for 2i/L-specific pluripotency factor binding, TET2 and H3K4me1. C_LIO_LIEnhancer hypomethylation coincides with increased expression of nearby and Capture Hi-C linked genes. C_LI

developmental biology↗

bioRxiv2021

TGFβ signalling is required to maintain pluripotency of human naïve pluripotent stem cells

The signalling pathways that maintain primed human pluripotent stem cells (hPSCs) have been well characterised, revealing a critical role for TGF{beta}/Activin/Nodal signalling. In contrast, the signalling requirements of naive human pluripotency have not been fully established. Here, we demonstrate that TGF{beta} signalling is required to maintain naive hPSCs. The downstream effector proteins - SMAD2/3 - bind common sites in naive and primed hPSCs, including shared pluripotency genes. In naive hPSCs, SMAD2/3 additionally bind to active regulatory regions near to naive pluripotency genes. Inhibiting TGF{beta} signalling in naive hPSCs causes the downregulation of SMAD2/3-target genes and pluripotency exit. Single-cell analyses reveal that naive and primed hPSCs follow different transcriptional trajectories after inhibition of TGF{beta} signalling. Primed hPSCs differentiate into neuroectoderm cells, whereas naive hPSCs transition into trophectoderm. These results establish that there is a continuum for TGF{beta} pathway function in human pluripotency spanning a developmental window from naive to primed states.

cell biology↗

bioRxiv2021

In vitro evaluation of the effect of mutations in primer binding sites on detection of SARS-CoV-2 by RT-qPCR

A number of RT-qPCR assays for the detection of SARS-CoV-2 have been published and are listed by the WHO as recommended assays. Furthermore, numerous commercial assays with undisclosed primer and probe sequences are on the market. As the SARS-CoV-2 pandemic progresses, the virus accrues mutations, which in some cases - as seen with the B.1.1.7 variant - can outperform and push back other strains of SARS-CoV-2. If mutations occur in primer or probe binding sites, this can impact RT-qPCR results and impede SARS-CoV-2 diagnostics. Here we tested the effect of primer mismatches on RT-qPCR performance in vitro using synthetic mismatch in vitro transcripts. The effects of the mismatches ranged from a shift in ct values from -0.13 to +7.61. Crucially, we found that a mismatch in the forward primer has a more detrimental effect for PCR performance than a mismatch in the reverse primer. Furthermore, we compared the performance of the original Charite RdRP primer set, which has several ambiguities, with a primer version without ambiguities and found that without ambiguities the ct values are ca. 3 ct lower. Finally, we investigated the shift in ct values observed with the Seegene Allplex kit with the B.1.1.7 SARS-CoV-2 variant and found a three-nucleotide mismatch in the forward primer of the N target.

molecular biology↗

bioRxiv2019

Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states

SO_SCPCAPUMMARYC_SCPCAPA complex and poorly understood interplay between 3D genome organisation, transcription factors and chromatin state underpins cell identity. To gain a systems-level understanding of this interplay, we generated a high-resolution atlas of annotated chromatin interactions in naive and primed human pluripotent stem cells and developed a network-graph approach to examine the atlas at multiple spatial scales. Investigating chromatin interactions as a network uncovered highly connected hubs that changed substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merged to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. Importantly, we identified state-specific differences in enhancer activity and interactivity that corresponded with widespread reconfiguration of transcription factor binding and target gene expression. These findings provide multilayered insights into the gene regulatory control of human pluripotency and our systems-based network approach could be applied broadly to uncover new principles of 3D genome organisation.

genomics↗

bioRxiv2019

Dppa2/4 target chromatin bivalency enabling multi-lineage commitment

Bivalent chromatin marks developmental promoters in pluripotent cells, yet their targeting and precise impact on lineage commitment remains unclear. We uncover Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as epigenetic priming factors, establishing chromatin bivalency. Single-cell transcriptomics and differentiation assays reveal Dppa2/4 double knockout embryonic stem cells fail to exit pluripotency and differentiate efficiently. Dppa2/4 associate with COMPASS and Polycomb complexes and are required to recruit and maintain their binding at a subset of developmentally important bivalent promoters which are characterised by low expression and poised RNA polymerase. Consequently, upon Dppa2/4 knockout, these dependent promoters gain DNA methylation and are unable to be activated upon differentiation. Our findings uncover a novel targeting principle for bivalency to developmental promoters, poising them for future lineage specific activation.

molecular biology↗

bioRxiv2019

Trophic variation within a piscivorous lake trout morph from Great Bear Lake, Canada: The initial step toward ecological specialization?

In a polymorphic species, stable differences in resource use are expected among ecotypes, and homogeneity in resource use is predicted within an ecotype. Yet, using a broad resource spectrum has been identified as a strategy for fishes living in unproductive northern environments, where food is patchily distributed and ephemeral. We investigated whether individual specialization of trophic resources occurred within the generalist piscivore ecotype of lake trout from Great Bear Lake, Canada, reflective of a form of diversity. Four distinct dietary patterns of resource use within the lake trout ecotype were detected from fatty acid composition, with some variation linked to spatial patterns within Great Bear Lake. Feeding habits of different groups within the ecotype were not associated with detectable morphological or genetic differentiation, suggesting that behavioral plasticity caused the trophic differences. A low level of genetic differentiation was detected between exceptionally large-sized individuals and other individuals. Investigating a geologically young system that displays high levels of intraspecific diversity and focusing on individual variation in diet suggested that individual trophic specialization can occur within an ecotype. The characterization of niche use among individuals, as done in this study, is necessary to understand the role that individual variation can play at the beginning of differentiation processes.

ecology↗

bioRxiv2019

Dietary vs non-dietary fatty acid profiles of lake trout morphs from Lake Superior and Great Bear Lake: Are fish really what they eat?

Fatty acids are well-established biomarkers used to characterize trophic ecology, food-web linkages, and the ecological niche of many different taxa. Most often, fatty acids that are examined include only those previously identified as "dietary" or "extended dietary" biomarkers. Fatty acids considered as non-dietary biomarkers, however, represent numerous fatty acids that can be extracted. Some studies may include non-dietary fatty acids (i.e., combined with dietary fatty acids), but do not specifically assess them, whereas in other studies, these data are discarded. In this study, we explored whether non-dietary biomarkers fatty acids can provide worthwhile information by assessing their ability to discriminate intraspecific diversity within and between lakes. Non-dietary fatty acids used as biomarkers delineated variation among regions, among locations within a lake, and among ecotypes within a species. Physiological differences that arise from differences in energy processing can be adaptive and linked to habitat use by a species ecotypes, and likely explains why non-dietary fatty acids biomarkers can be a relevant tool to delineate intraspecific diversity. Little is known about the non-dietary-mediated differences in fatty acid composition, but our results showed that non-dietary fatty acids biomarkers can be useful tool in identifying variation.

ecology↗

bioRxiv2019

Single cell multi-omics profiling reveals a hierarchical epigenetic landscape during mammalian germ layer specification

Formation of the three primary germ layers during gastrulation is an essential step in the establishment of the vertebrate body plan. Recent studies employing single cell RNA-sequencing have identified major transcriptional changes associated with germ layer specification. Global epigenetic reprogramming accompanies these changes, but the role of the epigenome in regulating early cell fate choice remains unresolved, and the coordination between different epigenetic layers is unclear. Here we describe the first single cell triple-omics map of chromatin accessibility, DNA methylation and RNA expression during the exit from pluripotency and the onset of gastrulation in mouse embryos. We find dynamic dependencies between the different molecular layers, with evidence for distinct modes of epigenetic regulation. The initial exit from pluripotency coincides with the establishment of a global repressive epigenetic landscape, followed by the emergence of local lineage-specific epigenetic patterns during gastrulation. Notably, cells committed to mesoderm and endoderm undergo widespread coordinated epigenetic rearrangements, driven by loss of methylation in enhancer marks and a concomitant increase of chromatin accessibility. In striking contrast, the epigenetic landscape of ectodermal cells is already established in the early epiblast. Hence, regulatory elements associated with each germ layer are either epigenetically primed or epigenetically remodelled prior to overt cell fate decisions during gastrulation, providing the molecular logic for a hierarchical emergence of the primary germ layers.\n\nHighlightsO_LIFirst map of mouse gastrulation using comprehensive single cell triple-omic analysis.\nC_LIO_LIExit from pluripotency is associated with a global repressive epigenetic landscape, driven by a sharp gain of DNA methylation and a gradual decrease of chromatin accessibility.\nC_LIO_LIDNA methylation and chromatin accessibility changes in enhancers, but not in promoters, are associated with germ layer formation.\nC_LIO_LIMesoderm and endoderm enhancers become open and demethylated upon lineage commitment.\nC_LIO_LIEctoderm enhancers are primed in the early epiblast and protected from the global repressive dynamics, supporting a default model of ectoderm commitment in vivo.\nC_LI

developmental biology↗

bioRxiv2018

Dppa2 and Dppa4 directly regulate the Dux driven zygotic transcriptional programme

The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of \"2C-like\" cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional programme is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional programme which is subsequently reinforced by Zscan4c.

molecular biology↗

bioRxiv2017

Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

genetics↗

bioRxiv2017

A non-catalytic role of TET3 promotes open chromatin and enhances global transcription

The methylcytosine dioxygenase Tet3 is highly expressed as a specific isoform in oocytes and zygotes but essentially absent from later stages of mouse preimplantation development. Here, we show that Tet3 expression promotes transdifferentiation of embryonic stem cells to trophoblast-like stem cells. By genome-wide analyses we demonstrate that TET3 associates with and co-occupies chromatin with RNA Polymerase II. Tet3 expression induces a global increase of transcription and total RNA levels, and its presence further enhances chromatin accessibility in regions open for transcription. This novel function of TET3 is not specific to the oocyte isoform, independent of its catalytic activity, the CXXC domain, or its interaction with OGT, and is localised in its highly conserved exon 4. We propose a more general role for TET3 promoting open chromatin and enhancing global transcription during changes of cellular identity, separate from its catalytic function.

developmental biology↗