bioRxiv Science⌕ Search

Biology subjects

Kaufman, E.

Publications and source records attributed to Kaufman, E..

4 recordsLinked to original sources

Polo-like kinase 1 maintains transcription and chromosomal accessibility during mitosis

Transcription persists at low levels in mitotic cells and plays essential roles in mitotic fidelity and chromosomal dynamics. However, the detailed regulatory network of mitotic transcription remains largely unresolved. Here, we report the novel role of Polo-like kinase 1 (Plk1) in maintaining mitotic transcription. Using 5-ethynyl uridine (5-EU) labeling of nascent RNAs, we found that Plk1 inhibition leads to significant downregulation of nascent transcription in prometaphase cells. Chromatin-localized Plk1 activity is required for transcription regulation and mitotic fidelity. Plk1 sustains global chromosomal accessibility in mitosis, especially at promoter and transcription start site (promoter-TSS) regions, facilitating transcription factor binding and ensuring proper transcriptional activity. We identified SMC4, a common subunit of condensin I and II, as a potential Plk1 substrate. Plk1 activity is fundamental to these processes across non-transformed and transformed cell lines, underscoring its critical role in cell cycle regulation. This study elucidates a novel regulatory mechanism of global mitotic transcription, advancing our understanding of cell cycle control. Significance StatementO_LICells retain a low level of transcription during mitosis, while the regulatory network and specific contributions of mitotic transcription are not well understood. C_LIO_LIWe identify Polo-like kinase 1 (Plk1) as a novel regulator of mitotic transcription, crucial for chromosome condensation, genome accessibility, and maintaining mitotic fidelity. C_LIO_LIThis study enhances our understanding of Plk1s multifaceted role in mitotic progression, advancing cell cycle regulation knowledge, and informing new cancer therapies development. C_LI

cell biology↗

Microbiota Dynamics in Lionfish (Pterois): Insights into Invasion and Establishment in the Mediterranean Sea

Lionfishes (Pterois spp.), originally native to the Indo-Pacific and Red Sea, have become one of the most invasive marine species globally, including the recent establishment in the Mediterranean Sea. This study investigates the microbiota of lionfish to explore its potential role in their invasion success and establishment. Using high-throughput sequencing and microbiota analyses, we characterized the species-specific core microbiome and identified habitat-specific markers across different regions (Red Sea, Mediterranean Sea, Caribbean, and aquarium populations) and organs. Focusing on the Mediterranean invasion, we tracked lionfish distribution and population dynamics along the Israeli coastline from 2017 to 2023, monitoring size, seasonal trends, and depth preferences. Our findings reveal that lionfish initially established themselves in deeper waters before expanding to shallower habitats, with a gradual increase in population size and body length over time. From a microbial aspect, we compared the microbiota of lionfish organs and identified a similar pattern (Photobacterium), to Earlier Lessepsian migrants fish species. This study provides novel insights into the interactions between microbiota and host ecology, shedding light on the mechanisms that may support the successful invasion. This study contributes to the understanding of lionfish invasion dynamics in the Mediterranean. It highlights the microbiota as an integral component for studying the ecological and biological mechanisms underpinning invasive species success and establishment of lionfish.

ecology↗

Structural and genetic diversity in the secreted mucins, MUC5AC and MUC5B

The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of MUC5AC and MUC5B by long-read sequencing and assembly of 206 human and 20 nonhuman primate (NHP) haplotypes. We find that human MUC5B is largely invariant (5761-5762aa); however, seven haplotypes have expanded VNTRs (6291-7019aa). In contrast, 30 allelic variants of MUC5AC encode 16 distinct proteins (5249-6325aa) with cysteine-rich domain and VNTR copy number variation. We grouped MUC5AC alleles into three phylogenetic clades: H1 (46%, [~]5654aa), H2 (33%, [~]5742aa), and H3 (7%, [~]6325aa). The two most common human MUC5AC variants are smaller than NHP gene models, suggesting a reduction in protein length during recent human evolution. Linkage disequilibrium (LD) and Tajimas D analyses reveal that East Asians carry exceptionally large MUC5AC LD blocks with an excess of rare variation (p<0.05). To validate this result, we used Locityper for genotyping MUC5AC haplogroups in 2,600 unrelated samples from the 1000 Genomes Project. We observed signatures of positive selection in H1 and H2 among East Asians and a depletion of the likely ancestral haplogroup (H3). In Africans and Europeans, H3 alleles show an excess of common variation and deviate from Hardy-Weinberg equilibrium, consistent with heterozygote advantage and balancing selection. This study provides a generalizable strategy to characterize complex protein coding VNTRs for improved disease associations.

genomics↗

Collecting-Gathering Biophysics of the Blackworm L. variegatus

Many organisms exhibit collecting and gathering behaviors as a foraging and survival method. Certain benthic macroinvertebrates are classified as collector-gatherers due to their collection of particulate matter as a food source, such as the aquatic oligochaete Lumbriculus variegatus (California blackworms). Blackworms demonstrate the ability to ingest organic and inorganic materials, including microplastics, but previous work has only qualitatively described their possible collecting behaviors for such materials. The mechanism through which blackworms consolidate discrete particles into a larger clumps remains unexplored quantitatively. By analyzing a group of blackworms in a large arena with an aqueous algae solution, we discover that their relative collecting efficiency is proportional to population size. Examining individual blackworms under a microscope reveals that both algae and microplastics physically adhere to the worms body due to external mucus secretions, which cause the materials to clump around the worm. We observe that this clumping reduces the worms exploration of its environment, potentially due to thigmotaxis. To validate the observed biophysical mechanisms, we create an active polymer model of a worm moving in a field of particulate debris with a short-range attractive force on its body to simulate its adhesive nature. We find that the attractive force increases gathering efficiency. This study offers insights into the mechanisms of collecting-gathering behavior, informing the design of robotic systems, as well as advancing our understanding the ecological impacts of microplastics on benthic invertebrates.

ecology↗