Biology subjects

Denholtz, M.

Publications and source records attributed to Denholtz, M..

4 recordsLinked to original sources

bioRxiv2021

Simons Collaborative Marine Atlas Project (Simons CMAP): an open-source portal to share, visualize and analyze ocean data

Simons Collaborative Marine Atlas Project (Simons CMAP) is an open-source data portal that interconnects large, complex, and diverse public data sets currently dispersed in different formats across different Oceanography discipline-specific databases. Simons CMAP is designed to streamline the retrieval of custom subsets of data, the generation of data visualizations, and the analyses of diverse data, thus expanding the power of these potentially underutilized data sets for cross-disciplinary studies of ocean processes. We describe a unified architecture that allows numerical model outputs, satellite products, and field observations to be readily shared, mined, and integrated regardless of data set size or resolution. A current focus of Simons CMAP is integration of physical, chemical, and biological data sets essential for characterizing the biogeography of key marine microbes across ocean basins and seasonal cycles. Using a practical example, we demonstrate how our unifying data harmonization plans significantly simplifies and allows for systematic data integration across all Simons CMAP data sets.

ecology↗

bioRxiv2019

Upon microbial challenge human neutrophils undergo rapid changes in nuclear architecture to orchestrate an immediate inflammatory gene program

Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior to encounter with bacteria, an armamentarium of inflammatory genes was positioned in a transcriptionally passive environment suppressing premature transcriptional activation. Upon microbial exposure, however, human neutrophils rapidly (<3 hours) repositioned the ensemble of pro-inflammatory genes towards the transcriptionally permissive compartment. We show that the repositioning of genes was closely associated with the swift recruitment of cohesin across the inflammatory enhancer landscape permitting an immediate transcriptional response upon bacterial exposure. These data reveal at the mechanistic level how upon microbial challenge human neutrophils undergo rapid changes in nuclear architecture to orchestrate an immediate inflammatory gene program.

genomics↗

bioRxiv2018

An inter-chromosomal transcription hub activates the unfolded protein response in plasma cells

Previous studies have indicated that the transcription signature of antibody-secreting cells is closely associated with the induction of the unfolded protein response pathway (UPR). Here we have used genome-wide and single cell analyses to examine the folding patterns of plasma cell genomes. We found that plasma cells adopt a cartwheel configuration and undergo large-scale changes in chromatin folding at genomic regions associated with a plasma cell specific transcription signature. During plasma cell differentiation, Blimp1 assembles into an inter-chromosomal transcription hub with genes associated with the UPR, biosynthesis of the endoplasmic reticulum (ER) as well as a cluster of genes linked with Alzheimers disease. We suggest that the assembly of the Blimp1-UPR-ER transcription hub permits the coordinate activation of a wide spectrum of genes that collectively establish plasma cell identity.

immunology↗

bioRxiv2017

Comprehensive characterization of neutrophil genome topology

Neutrophils are responsible for the first line of defense against invading pathogens. Their nuclei are uniquely structured as multiple lobes that establish a highly constrained nuclear environment. Here we found that neutrophil differentiation was not associated with large-scale changes in the number and sizes of topologically associating domains. However, neutrophil genomes were enriched for long-range genomic interactions that spanned multiple topologically associating domains. Population-based simulation of spherical and toroid genomes revealed declining radii of gyration for neutrophil chromosomes. We found that neutrophil genomes were highly enriched for heterochromatic genomic interactions across vast genomic distances, a process named super-contraction. Super-contraction involved genomic regions located in the heterochromatic compartment in both progenitors and neutrophils or genomic regions that switched from the euchromatic to the heterochromatic compartment during neutrophil differentiation. Super-contraction was accompanied by the repositioning of centromeres, pericentromeres and Long-Interspersed Nuclear Elements (LINEs) to the neutrophil nuclear lamina. We found that Lamin-B Receptor expression was required to attach centromeric and pericentromeric repeats but not LINE-1 elements to the lamina. Differentiating neutrophils also repositioned ribosomal DNA and mini-nucleoli to the lamina: a process that was closely associated with sharply reduced ribosomal RNA expression. We propose that large-scale chromatin reorganization involving super-contraction and recruitment of heterochromatin and nucleoli to the nuclear lamina facilitate the folding of the neutrophil genome into a confined geometry imposed by a multi-lobed nuclear architecture.

molecular biology↗