Distinct IL-1α-responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner

How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1α induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF-κB at regions that are highly enriched for inflammatory disease-relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL-1α-inducible IL8 and CXCL1-3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL-1α/TAK1-inducible manner. Microdeletions of p65-binding sites in either of the two enhancers impair NF-κB recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher-order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 “master” enhancer in the regulation of sustained IL-1α signaling, as well as for IL-8 and IL-6 secretion. CRISPR-guided transactivation of the IL8 locus or cross-TAD regulation by TNFα-responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF-κB

Fast X-ray microfluorescence imaging with submicrometer-resolution integrating a Maia detector at beamline P06 at PETRA III

The high brilliance of third-generation synchrotron sources increases thedemand for faster detectors to utilize the available flux. The Maia detector is anadvanced imaging scheme for energy-dispersive detection realising dwell timesper image-pixel as low as 50 ms and count rates higher than 10 106 s1. In thisarticle the integration of such a Maia detector in the Microprobe setup ofbeamline P06 at the storage ring PETRA III at the Deutsches Elektronen-Synchrotron (DESY) in Hamburg, Germany, is described. The analyticalperformance of the complete system in terms of rate-dependent energyresolution, scanning-speed-dependent spatial resolution and lower limits ofdetection is characterized. The potential of the Maia-based setup is demonstratedby key applications from materials science and chemistry, as well asenvironmental science with geological applications and biological questions thathave been investigated at the P06 beamline

Distinct IL-1 alpha-responsive enhancers promote acute and coordinated changes in chromatin topology in a hierarchical manner

How cytokine-driven changes in chromatin topology are converted into gene regulatory circuits during inflammation still remains unclear. Here, we show that interleukin (IL)-1 alpha induces acute and widespread changes in chromatin accessibility via the TAK1 kinase and NF-kappa B at regions that are highly enriched for inflammatory disease-relevant SNPs. Two enhancers in the extended chemokine locus on human chromosome 4 regulate the IL-1 alpha-inducible IL8 and CXCL1-3 genes. Both enhancers engage in dynamic spatial interactions with gene promoters in an IL-1 alpha/TAK1-inducible manner. Microdeletions of p65-binding sites in either of the two enhancers impair NF-kappa B recruitment, suppress activation and biallelic transcription of the IL8/CXCL2 genes, and reshuffle higher-order chromatin interactions as judged by i4C interactome profiles. Notably, these findings support a dominant role of the IL8 master enhancer in the regulation of sustained IL-1 alpha signaling, as well as for IL-8 and IL-6 secretion. CRISPR-guided transactivation of the IL8 locus or cross-TAD regulation by TNF alpha-responsive enhancers in a different model locus supports the existence of complex enhancer hierarchies in response to cytokine stimulation that prime and orchestrate proinflammatory chromatin responses downstream of NF-kappa B

Building S.C.A.D.A. Systems in Scientific Installations with Sardana and Taurus

International audienceSardana and Taurus form a python software suite for Supervision, Control and Data Acquisition (SCADA) optimized for scientific installations. Sardana and Taurus are open source and deliver a substantial reduction in both time and cost associated to the design, development and support of control and data acquisition systems. The project was initially developed at ALBA and later evolved to an international collaboration driven by a community of users and developers from ALBA, DESY, MAXIV and Solaris as well as other institutes and private companies. The advantages of Sardana for its adoption by other institutes are: free and open source code, comprehensive workflow for enhancement proposals, a powerful environment for building and executing macros, optimized access to the hardware and a generic Graphical User Interface (Taurus) that can be customized for every application. Sardana and Taurus are currently based on the Tango Control System framework but also capable to inter-operate to some extend with other control systems like EPICS. The software suite scales from small laboratories to large scientific institutions, allowing users to use only some parts or employ it as a whole