Systemic lupus erythematosus (SLE) is characterized by an accelerated apoptosis of peripheral lymphocytes and an impairment of the clearance of apoptotic cells. Since changes in DNA methylation and in deoxycytosine and deoxyguanine (GC) content have been shown to enhance the potential of DNA to activate murine and human B lymphocytes, we tested the capacity of lymphocytes undergoing apoptosis (under conditions that mimic the deletion of self-reactive cells after antigen receptor engagement) to generate nucleosomes with a particular base composition. Using two cell culture systems and four apoptosis triggers, we found an increase of deoxymethylcytosine in fragmented chromosomal DNA of apoptotic B and T lymphocytes. However, this increase was not associated with modulation of DNA (cytosine-5) methyltransferase, the enzyme that methylates eukaryotic DNA, which suggests that the changes in DNA methylation patterns are not linked to the process of de novo DNA methylation during cell death. In addition, we could not detect a unique methylation pattern in highly repetitive Alu sequences present in the human genome of SLE subjects, as compared with controls. However, the abnormal DNA methylation of apoptotic nucleosomes was associated with an unusual pattern of nuclease-resistant, GC-rich regions in these DNA fragments. We propose that the combination of an accelerated apoptosis with a defect in the clearance of apoptotic cells results in release of increased amounts of nucleosomes with abnormally methylated, GC-rich DNA and provides an autologous stimulation that could bypass tolerance to self in systemic autoimmune diseases. These findings support the concept that the structure and dynamics of nucleosomes are critical in determining their immunogenicity in SLE.
Protein phosphatase 1 is regulated by the interaction between a catalytic subunit (PP1c) and multiple interacting proteins that allow the specific dephosphorylation of diverse cellular targets. This communication proposes to use the simultaneous presence of distinct consensus PP1c docking motifs R/K-x(0,1)-V-x-F and F-x-x-R/K-x-R/K as a signature to identify proteins putatively interacting with the PP1c. To develop this concept, we propose a new website, http://pp1signature.pasteur.fr, which allows the identification of putative PP1-interacting proteins containing the two distinct PP1c docking consensus motifs represented in the Swissprot library. To validate the new concept of signature, we were able to characterise, by co-immunoprecipitation, four new PP1c interacting proteins randomly selected from the database in our website. To cite this article: A.
Background: Bioinformaticians routinely use multiple software tools and data sources in their day-to-day work and have been guided in their choices by a number of cataloguing initiatives. The ELIXIR Tools and Data Services Registry (bio.tools) aims to provide a central information point, independent of any specific scientific scope within bioinformatics or technological implementation. Meanwhile, efforts to integrate bioinformatics software in workbench and workflow environments have accelerated to enable the design, automation, and reproducibility of bioinformatics experiments. One such popular environment is the Galaxy framework, with currently more than 80 publicly available Galaxy servers around the world. In the context of a generic registry for bioinformatics software, such as bio.tools, Galaxy instances constitute a major source of valuable content. Yet there has been, to date, no convenient mechanism to register such services en masse. Findings: We present ReGaTE (Registration of Galaxy Tools in Elixir), a software utility that automates the process of registering the services available in a Galaxy instance. This utility uses the BioBlend application program interface to extract service metadata from a Galaxy server, enhance the metadata with the scientific information required by bio.tools, and push it to the registry. Conclusions: ReGaTE provides a fast and convenient way to publish Galaxy services in bio.tools. By doing so, service providers may increase the visibility of their services while enriching the software discovery function that bio.tools provides for its users. The source code of ReGaTE is freely available on Github at https://github.com/C3BI-pasteur-fr/ReGaTE.
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