Eastwood, N. | Search bioRxiv

bioRxiv2026

ARID1A orchestrates the activity of FOXA1 and AP-2 transcription factors in lobular breast cancer cells

Mutations in components of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodelling complex are among the most common genetic alterations in human cancers, yet their functional consequences are difficult to predict as they are highly context-dependent. ARID1A, a core subunit of the canonical BAF complex, is the most frequently mutated SWI/SNF gene and is recurrently altered in breast cancer, with a notable enrichment in the lobular carcinoma subtype. While previous studies in ductal breast cancer have linked ARID1A loss to deregulated oestrogen receptor (ER) signalling and endocrine resistance through its association with the pioneer factor FOXA1, the role of ARID1A in lobular cancer remains poorly understood. Here, we define the genomic, transcriptomic, and chromatin accessibility landscapes governed by ARID1A in lobular breast cancer cells. We show that ARID1A and its catalytic partner SMARCA4 co-occupy distal regulatory regions enriched for forkhead and AP-2 transcription factor motifs. ARID1A depletion leads predominantly to loss of chromatin accessibility at these putative enhancer regions and downregulation of associated genes, indicating a primary role in maintaining a permissive regulatory landscape. Extensive co-binding and reciprocal dependencies between ARID1A, FOXA1, and AP-2 transcription factors reveal a coordinated regulatory network distinct from that observed in ductal breast cancers. ARID1A loss does not impair ER-mediated transcriptional responses in the lobular subtype but instead alters basal expression of a subset of oestrogen-responsive genes. Importantly, ARID1A, FOXA1, and AP-2 jointly regulate genes implicated in skeletal system development and bone metastasis, mirroring mutational patterns observed in lobular breast cancer patient datasets. These findings highlight a unique ARID1A-centred transcriptional programme in lobular breast cancer with potential implications for metastatic behaviour and therapeutic vulnerability.

Cancer Biology↗

bioRxiv2023

100 years of anthropogenic impact causes changes in freshwater functional biodiversity

Despite efforts from scientists and regulators, biodiversity is declining at an alarming rate. Unless we find transformative solutions to preserve biodiversity, future generations may not be able to enjoy natures services. We have developed a conceptual framework that establishes the links between biodiversity dynamics and abiotic change through time and space using artificial intelligence. Here, we apply this framework to a freshwater ecosystem with a known history of human impact and study 100 years of community-level biodiversity, climate change and chemical pollution trends. We apply explainable network models with multimodal learning to community-level functional biodiversity measured with multilocus metabarcoding, to establish correlations with biocides and climate change records. We observed that the freshwater community assemblage and functionality changed over time without returning to its original state, even if the lake partially recovered in recent times. Insecticides and fungicides, combined with extreme temperature events and precipitation, explained up to 90% of the functional biodiversity changes. The community-level biodiversity approach used here reliably explained freshwater ecosystem shifts. These shifts were not observed when using traditional quality indices (e.g. Trophic Diatom Index). Our study advocates the use of high throughput systemic approaches on long-term trends over species-focused ecological surveys to identify the environmental factors that cause loss of biodiversity and disrupt ecosystem functions.

ecology↗