Biology subjects

Ettinger, A.

Publications and source records attributed to Ettinger, A..

5 recordsLinked to original sources

bioRxiv2026

Aquarius RNA helicase Protects Pluripotent Stem Cell Identity

Pluripotent stem cells must reconcile rapid replication with a highly dynamic transcriptional program, creating an inherent susceptibility to transcription-replication conflicts (TRCs). We demonstrate that embryonic stem cells (ESCs) operate in a "resilient" replication mode, tolerating high genomic traffic through the constitutive upregulation of R-loop and TRC resolution pathways. Through a targeted functional screen, we identify the RNA helicase Aquarius (AQR) as an essential safeguard of this state. AQR depletion downregulates these resolution factors, collapsing this stress-resistant program and driving ESCs into unstable, heterogenous states, marked by increased transcriptional entropy and cell-to-cell noise. Mechanistically, we show that key identity-defining genes are preferentially located within R-loop and TRC prone regions, making them uniquely vulnerable to AQR depletion. Our findings establish AQR as a critical governor of transcriptional fidelity, demonstrating that genomic resilience is fundamental to maintaining pluripotent cell identity.

cell biology↗

bioRxiv2025

H3K4 methylation-promoted transcriptional memory ensures faithful zygotic genome activation and embryonic development

In the life of a vertebrate embryo, gene expression is initiated for the first time at zygotic genome activation (ZGA). Maternally expressed transcription factors present in the embryo are essential for this process. However, it is unknown if active chromatin modifications established in the gamete are propagated in the embryo as an epigenetic memory to support ZGA and embryonic development. Here, we provide evidence that in Xenopus laevis, H3K4 methylation provides an epigenetic memory of active chromatin states. We show that this is required for faithful zygotic genome activation and successful embryonic development. Chromatin configurations of promoters displaying high H3K4me3 intensity and breadth, alongside DNA hypomethylation and increased GC content, are propagated from the gametes to the embryo across multiple cell divisions and a transcriptionally quiescent phase in early development. We show that this transmission of H3K4 methylation is essential for precise zygotic genome activation and expression of key pioneer ZGA transcription factors Pou5f3.2 and Sox3. Finally, we demonstrate that the H3K4 methyltransferases Kmt2b and Cxxc1 ensure transcription-independent propagation of H3K4me3 and proper zygotic gene expression. In summary, our study establishes the role of H3K4 methylation in maintaining memory of active chromatin states in Xenopus embryos and reveals its importance for successful embryonic development.

developmental biology↗

bioRxiv2023

Microclimate buffering varies across forest types during an extreme heat event

Increasing temperatures and extreme heat episodes have become more common with climate change. While forests are known to be buffered from increasing temperatures compared to non-forested areas, whether this buffering is maintained under extreme temperature events, how such events influence forests, and how forest organisms respond to extreme heat is relatively unknown. Here we assess the effects of an extreme heat event (the Pacific Northwest (PNW) heatdome in June 2021) on forest microclimates, forests, and the organisms living within them. We first asked how the PNW heatdome affected microclimates in forests with differing canopy cover (including non-forests) and found that the buffering capacity of forests is greater under denser canopies, even under extreme heat events. We then combined this information with organismal temperature tolerance curves for 12 relevant species and found that canopy buffering can minimize the negative impacts of even extreme heat events on understory organisms, with greater canopy density providing greater microclimate moderation. Finally, we analyzed seasonal NDVI trends in recent years, and found signs of canopy stress following the extreme 2021 heat event. In all, this suggests that although forest canopies may buffer the negative effects of extreme heat events on understory organisms, a greater frequency of extreme heat events may threaten this capacity by damaging forest canopies.

ecology↗

bioRxiv2023

The CGG triplet repeat binding protein 1 counteracts DNA secondary structure-induced transcription-replication conflicts

Short tracts of trinucleotide repeats with less than 10 repeats are found frequently throughout the genome without any apparent negative impact on DNA replication fork progression or transcription elongation. CGG binding protein 1 (CGGBP1) binds to CGG triplet repeats and has been implicated in multiple cellular processes such as transcription, replication and DNA damage. Here, we show that CGGBP1 binds to human gene promoter sites prone to G-quadruplex and R-loop secondary structure formation. Altering CGGBP1 levels results in the accumulation of R-loops and causes a defect in transcriptional elongation by RNA polymerase II, which subsequently leads to replication fork stalling and transcription-replication conflicts. Together, our work shows that short trinucleotide repeats are a source of genome-destabilizing secondary structures and cells rely on specific DNA-binding factors to maintain proper transcription and replication progression at short trinucleotide repeats.

cell biology↗

bioRxiv2017

Local Control of Intracellular Microtubule Dynamics by End Binding Protein 1 (EB1) Photo-Dissociation

Dynamic remodelling of the microtubule cytoskeleton and local interactions with intracellular targets are central to many polarized cell biological processes, an idea first formalized as search-and-capture hypothesis three decades ago1. However, because of the rapid timescale of microtubule polymerization dynamics, it is difficult to directly ask how, when and where dynamic microtubules participate in specific biological processes. Here, we employ a blue light-sensitive interaction with the oat phototropin LOV2 domain2 to generate a photo-inactivated variant of the microtubule end-binding protein EB1, a small adaptor that is central to the interaction of functionally and structurally diverse proteins with growing microtubule ends3,4, that can replace endogenous EB1 function. Acute and reversible blue light-mediated n-EB1 photo-dissociation allows spatially and temporally precise control of intracellular microtubule polymerization dynamics. In addition to demonstrating that neither the GTP cap nor the MT polymerase CKAP5 are sufficient to sustain persistent MT polymerization at physiological growth rates, our data illustrate accurate subcellular control of a freely diffusible, cytoplasmic protein at the second and micrometer scale. This novel design may serve as a template for precise control of many other intracellular protein activities.

cell biology↗