Biology subjects

Wilson, P. D.

Publications and source records attributed to Wilson, P. D..

5 recordsLinked to original sources

bioRxiv2026

Cooperative FOXA1-HNF4A binding emerges from motif spacing and nucleosome architecture

The pioneer factor hypothesis posits that specialized transcription factors access nucleosomal DNA to enable binding of secondary factors, implying a hierarchical mechanism of chromatin opening. However, recent evidence indicates that cooperative binding between pioneer and non-pioneer factors can occur in a context-dependent manner. Here we define the sequence and chromatin features that specify cooperative binding between FOXA1 and HNF4A. Using dual-induction of FOXA1 and HNF4A in naive cells, which lack endogenous expression of either factor, we identify a class of genomic sites that require both factors for binding and reside in initially inaccessible chromatin. A dual-head convolutional neural network finds no novel composite motif at these sites, instead implicating motif arrangement as the distinguishing feature. Cooperative loci are enriched for FOXA1-HNF4A motif pairs spaced 15-60 bp apart, a soft-syntax grammar consistent with nucleosome-mediated cooperativity. This spacing signature recurs at endogenously co-bound sites in HepG2 cells and primary fetal hepatocytes. Using a multiplexed in vitro nucleosome-binding assay (Pioneer-seq), we show that FOXA1 binds nucleosomal DNA more strongly than HNF4A across positions, and that cooperative binding strength on natural nucleosome sequences is predicted primarily by the position of the FOXA1 motif relative to the nucleosome dyad. Together, these results support a model in which positioned nucleosomes act as scaffolds that facilitate cooperative transcription factor binding through spatial motif organization, rather than a barrier one factor clears for the other.

genomics↗

bioRxiv2022

How exposure to land use impacts and climate change may prune the tetrapod tree of life

Human domination of landscapes is a key driver of biodiversity loss, with the fingerprint of climate change becoming increasingly pronounced. Frameworks and tools for identifying threats to biodiversity are required to meet Post-2020 Global Biodiversity Framework targets for 2030 that call for, among other things, reducing or halting species extinction rates (1). Hence, we compiled a phylogenetic tree for terrestrial tetrapods, mapped hotspots of geographically restricted and evolutionarily distinct lineages, and identified which hotspots may simultaneously face the highest magnitudes of land use impacts and climate change. Across a quarter of Earths surface, hotspots contain the entire ranges of 45% of tetrapods, representing 39% of terrestrial tetrapod evolutionary heritage. By 2070, we estimate 8-13% of this heritage to occur entirely within hotspots highly exposed to climate change, with 13-29% of hotspots projected to experience high exposure to both stressors simultaneously. Most hotspots at highest risk occur in countries least able to take action. Our analysis highlights the need for global ambition and coordination to avoid catastrophic loss of tetrapod evolutionary heritage.

ecology↗

bioRxiv2021

Emerging harmful algal blooms caused by distinct seasonal assemblages of the toxic diatom Pseudo-nitzschia in Narragansett Bay, RI, USA

The diatom Pseudo-nitzschia produces the neurotoxin domoic acid (DA) that bioaccumulates in shellfish, causing illness in humans and marine animals upon ingestion. In 2017, high levels of DA in shellfish meat closed shellfish harvest in Narragansett Bay (NBay), Rhode Island for the first time in history, although abundant Pseudo-nitzschia have been observed for over 50 years. What caused these events is unknown: whether an environmental factor altered endemic Pseudo-nitzschia physiology or new DA-producing strain(s) were introduced. To investigate, we conducted weekly sampling from 2017-2019 to compare with 2016 precautionary closure and 2017 closure samples. Particulate DA was quantified by highly sensitive LC-MS/MS and correlated with environmental metadata. Pseudo-nitzschia were identified using high-throughput rDNA sequencing, yielding a detailed understanding of distinct seasonal multi-species assemblages. Low DA was detected throughout 2017-2019, except in recurring peaks in the fall and early summer. Fall DA peaks contained toxigenic species (P. pungens var. pungens, P. multiseries, P. calliantha, and P. subpacifica) as well as a novel P. americana taxon. Fewer species were present during summer DA peaks including toxigenic P. multiseries, P. plurisecta, and P. delicatissima. Most 2017 closure samples contained P. australis. Our data showed P. australis as infrequent but particularly concerning. Recurring Pseudo-nitzschia assemblages were driven by seasonal temperature changes and DA correlated with low dissolved inorganic nitrogen. Thus, the NBay closures were likely caused by resident assemblages dependent on nutrient status as well as the episodic introductions of species that may be a result of oceanographic and climactic shifts.

ecology↗

bioRxiv2020

Ankhd1 enhances polycystic kidney disease development via promoting proliferation and fibrosis.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disorder resulting in 10% of patients with renal failure. The molecular events responsible for the relentless growth of cysts are not defined. Thus, identification of novel drivers of ADPKD may lead to new therapies. Ankyrin Repeat and Single KH domain-1 (ANKHD1) controls cancer cell proliferation, yet its role in ADPKD is unexplored. Here, we present the first data that identify ANKHD1 as a driver of proliferative growth in cellular and mouse models of ADPKD. Using the first Ankhd1-deficient mice, we demonstrate that Ankhd1 heterozygosity potently reduces cystic growth and fibrosis, in a genetically orthologous mouse model of ADPKD. We performed transcriptome-wide profiling of patient-derived ADPKD cells with and without ANKHD1 siRNA silencing, revealing a major role for ANKHD1 in the control of cell proliferation and matrix remodelling. We validated the role of ANKHD1 in enhancing proliferation in patient-derived cells. Mechanistically ANKHD1 promotes STAT5 signalling in ADPKD mice. Hence, ANKHD1 is a novel driver of ADPKD, and its inhibition may be of therapeutic benefit.

molecular biology↗

bioRxiv2019

Binned Relative Environmental Change Indicator (BRECI): A tool to communicate the nature of differences between environmental niche model outputs

Niche models are now widely used in many branches of the biological sciences and are often used to contrast the distribution of favourable environments between regions or under changes in environmental conditions such as climate change. Evaluating model performance and selecting optimal models is now accepted as best-practice, and a number of methods are available assist this process. One aspect of ENM application which has not received as much attention is developing methods to communicate the degree and nature of changes between model outputs (typically as raster maps). The method described in this paper, Binned Relative Environmental Change Index (BRECI), seeks to address this shortfall in communicating model results.

ecology↗