Biology subjects

Nagy, D.

Publications and source records attributed to Nagy, D..

3 recordsLinked to original sources

bioRxiv2023

Identification of mammalian transcription factors that bind to inaccessible chromatin

Transcription factors (TFs) are proteins that affect gene expression by binding to regulatory regions of DNA in a sequence specific manner. The binding of TFs to DNA is controlled by many factors, including the DNA sequence, concentration of TF, chromatin accessibility and co-factors. Here, we systematically investigated the binding mechanism of hundreds of TFs by analysing ChIP-seq data with our explainable statistical model, ChIPanalyser. This tool uses as inputs the DNA sequence binding motif; the capacity to distinguish between strong and weak binding sites; the concentration of TF; and chromatin accessibility. We asked whether TFs preferred to bind to DNA in open or dense chromatin conformation and found that approximately one third of TFs are predicted to bind the genome in a DNA accessibility independent fashion. Our model predicted this to be the case when the TF binds to its strongest binding regions in the genome, and only a small number of TFs have the capacity to bind dense chromatin at their weakest binding regions, such as CTCF USF2 and CEBPB. Our study demonstrated that the binding of hundreds of human and mouse TFs is predicted by ChIPanalyser with high accuracy and showed that many TFs can bind dense chromatin.

genomics↗

bioRxiv2021

Resilience of riparian vegetation composition and diversity following cessation of livestock grazing in northeastern Oregon, USA

Riparian ecosystem restoration has been accomplished through exclusion of livestock using corridor fencing along hundreds of kilometers of streams in the western USA, for the benefit of riparian-obligate wildlife and endangered fishes. Yet few studies have evaluated shifts in the vegetation composition and diversity following the cessation of livestock impacts. We sampled riparian vegetation composition along 11-paired grazed and ungrazed (exclosed) stream reaches in northeastern Oregon, USA. Exclosure ages ranged from 2 to >30 years and grazing treatments varied from light grazing every one out of three years to heavy season-long grazing. Species richness and diversity was higher in the ungrazed reaches (p =0.002). The abundance of native sedges (Carex spp.) and broad-leaved forbs were also significantly (p < 0.05) greater in ungrazed areas. In contrast, exotic species adapted to grazing such as Poa pratensis and Trifolium repens were more abundant in grazed stream reaches. The prevalence of hydrophytic species significantly increased (p [≤] 0.01) in ungrazed reaches, (based on wetland species indicator scores), indicating that wetland-dominated communities within the ungrazed stream reaches were replacing ones adapted to drier environments. The increased abundance of facultative and wetland-obligate species in ungrazed reaches compared to grazed reaches suggests that livestock grazing exacerbates those climate change effects also leading to warmer and drier conditions. Further, riparian-obligate shrub cover along the streambank was higher in 7 of 8 exclosures that were older than 5 years. As a restoration approach the inherent resilience of riparian ecosystems exhibited in ungrazed riparian zones suggest positive feedbacks to other beneficial ecosystem processes such as increased species and habitat diversity, increased carbon sequestration, enhanced allochthonous inputs and greater sediment retention, that would affect the aquatic and terrestrial biota, water quality, and stream morphology.

ecology↗

bioRxiv2020

Developing mammary terminal duct lobular units have a dynamic mucosal and stromal immune microenvironment

The human breast and ovine mammary gland undergo a striking degree of postnatal development, leading to formation of terminal duct lobular units (TDLUs). In this study we interrogated aspects of sheep TDLU growth to increase understanding of ovine mammogenesis and as a model for the study of breast development. Mammary epithelial proliferation is significantly higher in lambs less than two months old than in peri-pubertal animals. Ki67 expression is polarized to the leading edge of the developing TDLUs. Intraepithelial ductal macrophages exhibit striking periodicity and significantly increased density in lambs approaching puberty. Stromal macrophages are more abundant centrally than peripherally. The developing ovine mammary gland is infiltrated by intraepithelial and stromal T lymphocytes that are significantly more numerous in older lambs. In the stroma, hotspots of Ki67 expression colocalize with large aggregates of lymphocytes and macrophages. Multifocally these aggregates exhibit distinct organization consistent with tertiary lymphoid structures. The lamb mammary gland thus exhibits a dynamic mucosal and stromal immune microenvironment and, as such, constitutes a valuable model system that provides new insights into postnatal breast development. Summary statementDevelopment of terminal duct lobular units in the sheep mammary gland involves distinct growth phases and macrophage and lymphocyte fluxes. Tertiary lymphoid structures are present subjacent to the mucosal epithelium.

developmental biology↗