Presenter: Rushikesh Deshpande
Paper: Protein Arginine Methyltransferase 4 (PRMT4) mediates lymphopenia in experimental sepsis
Authors: Yandong Lai, Xiuying Li, Tiao Li, Yan Chen, Chen Long, Toru Nyunoya, Kong Chen,Georgios D. Kitsios,Seyed Mehdi Nouraie,Yingze Zhang, Bryan J. McVerry, Janet S. Lee,Rama K. Mallampalli, and Chunbin Zou
Onehallmark of sepsis is a reduced number of lymphocytes, termed lymphopenia,that occurs from decreased lymphocyte proliferation or increased cell death contributing to immune suppression. Histone modification enzymes regulate immunity by epigenetically modulating chromatin architecture, however, the role of these enzymes in lymphopenia remains elusive. In this study, we identified that a chromatin modulator Protein Arginine N-methyltransferase 4/Coactivator-Associated Arginine Methyltransferase 1 (PRMT4/ CARM1) that is elevated systemically inseptic patients and experimental sepsis, and is crucialfor inducing T-lymphocyte apoptosis.An E3 ubiquitin ligase SCFFBXO9 docks on PRMT4 via a phosphodegron to ubiquitinate the protein at K228 for ubiquitin proteasomal degradation. High PRMT4 expression resulted from reduced levels of SCFFBXO9 that led to increased lymphocyte cell death after Escherichia coliorlipopolysaccharide(LPS) exposure. Ectopic expression of PRMT4 protein caused substantially mphocytedeathvia caspase 3 mediated cell death signaling, and knockout of PRMT4 abolished LPS mediated lymphocyte cell death. PRMT4 inhibition with a small molecule compound attenuated lymphocyte death in complementary models of sepsis. These findings demonstrate a previously uncharacterized role of a key chromatin modulator in lymphocytesurvival that may shed light on devising unique therapeutic modalities to lessen severity of septic immunosuppression.
Presenter: Qi Wei
Paper: Maternal vitamin C regulates reprogramming of DNA methylation and germline development
Authors: Stephanie P. Ditroia, Michelle Percharde, Marie-Justine Guerquin, estelle Wall, evelyne Collignon, Kevin t. ebata, Kathryn Mesh, Swetha Mahesula, Michalis Agathocleous, Diana J. Laird, Gabriel Livera & Miguel Ramalho-Santos
Abstract: Development is often assumed to be hardwired in the genome, but several lines of evidence indicate that it is susceptible to environmental modulation with potential long-term consequences, including in mammals1,2. The embryonic germline is of particular interest because of the potential for intergenerational epigenetic effects. The mammalian germline undergoes extensive DNA demethylation3–7 that occurs in large part by passive dilution of methylation over successive cell divisions, accompanied by active DNA demethylation by TET enzymes3,8–10. TET activity has been shown to be modulated by nutrients and metabolites, such as vitamin C11–15. Here we show that maternal vitamin C is required for proper DNA demethylation and the development of female fetal germ cells in a mouse model. Maternal vitamin C deficiency does not affect overall embryonic development but leads to reduced numbers of germ cells, delayed meiosis and reduced fecundity in adult offspring. The transcriptome of germ cells from vitamin-C-deficient
embryos is remarkably similar to that of embryos carrying a null mutation in Tet1. Vitamin C deficiency leads to an aberrant DNA methylation profile that includes incomplete demethylation of key regulators of meiosis and transposable elements. These findings reveal that deficiency in vitamin C during gestation partially recapitulates loss of TET1, and provide a potential intergenerational mechanism for adjusting fecundity to environmental conditions
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Last Updated On Friday, September 20, 2019 by Orbell, Adam W
Created On Friday, September 20, 2019
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