Rockefeller University

About: Rockefeller University is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Gene. The organization has 15867 authors who have published 32938 publications receiving 2940261 citations. The organization is also known as: Rockefeller University & Rockefeller Institute.

Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB

Abstract: Polycomb group (PcG) proteins are transcriptional repressors that modify chromatin and regulate important developmental genes. One chromatin-modifying activity associated with Polycomb is an enzyme that ubiquitinates histone H2A. Here, Scheuermann et al. find a Drosophila PcG complex with H2A deubiquitination activity that is important for gene repression in vivo. Polycomb gene silencing may thus involve a dynamic balance between H2A ubiquitination and deubiquitination. Polycomb group (PcG) proteins are transcriptional repressors that modify chromatin and regulate important developmental genes. One PcG-associated, chromatin-modifying activity is an enzyme that ubiquitinates histone H2A of chromatin. Here, a fruitfly PcG complex that is associated with H2A deubiquitination, and thereby with gene repression, is identified. PcG-mediated gene silencing might thus involve a dynamic balance between ubiquitination and deubiquitination of H2A. Polycomb group (PcG) proteins are transcriptional repressors that control processes ranging from the maintenance of cell fate decisions and stem cell pluripotency in animals to the control of flowering time in plants1,2,3,4,5,6. In Drosophila, genetic studies identified more than 15 different PcG proteins that are required to repress homeotic (HOX) and other developmental regulator genes in cells where they must stay inactive1,7,8. Biochemical analyses established that these PcG proteins exist in distinct multiprotein complexes that bind to and modify chromatin of target genes1,2,3,4. Among those, Polycomb repressive complex 1 (PRC1) and the related dRing-associated factors (dRAF) complex contain an E3 ligase activity for monoubiquitination of histone H2A (refs 1–4). Here we show that the uncharacterized Drosophila PcG gene calypso encodes the ubiquitin carboxy-terminal hydrolase BAP1. Biochemically purified Calypso exists in a complex with the PcG protein ASX, and this complex, named Polycomb repressive deubiquitinase (PR-DUB), is bound at PcG target genes in Drosophila. Reconstituted recombinant Drosophila and human PR-DUB complexes remove monoubiquitin from H2A but not from H2B in nucleosomes. Drosophila mutants lacking PR-DUB show a strong increase in the levels of monoubiquitinated H2A. A mutation that disrupts the catalytic activity of Calypso, or absence of the ASX subunit abolishes H2A deubiquitination in vitro and HOX gene repression in vivo. Polycomb gene silencing may thus entail a dynamic balance between H2A ubiquitination by PRC1 and dRAF, and H2A deubiquitination by PR-DUB.

Food web patterns and their consequences

Abstract: A food web is a map that describes which kinds of organisms in a community eat which other kinds. A web helps picture how a community is put together and how it works. Although webs were often initially reported in despair at ever understanding ecological complexity, recently discovered widespread patterns in the shapes of webs, and theoretical explanations for these patterns, indicate that webs are orderly and intelligible, and have some foreseeable consequences for the dynamics of communities.

CD25+ CD4+ T Cells, Expanded with Dendritic Cells Presenting a Single Autoantigenic Peptide, Suppress Autoimmune Diabetes

Abstract: In the nonobese diabetic (NOD) mouse model of type 1 diabetes, the immune system recognizes many autoantigens expressed in pancreatic islet β cells. To silence autoimmunity, we used dendritic cells (DCs) from NOD mice to expand CD25+ CD4+ suppressor T cells from BDC2.5 mice, which are specific for a single islet autoantigen. The expanded T cells were more suppressive in vitro than their freshly isolated counterparts, indicating that DCs from autoimmune mice can increase the number and function of antigen-specific, CD25+ CD4+ regulatory T cells. Importantly, only 5,000 expanded CD25+ CD4+ BDC2.5 T cells could block autoimmunity caused by diabetogenic T cells in NOD mice, whereas 105 polyclonal, CD25+ CD4+ T cells from NOD mice were inactive. When islets were examined in treated mice, insulitis development was blocked at early (3 wk) but not later (11 wk) time points. The expanded CD25+ CD4+ BDC2.5 T cells were effective even if administered 14 d after the diabetogenic T cells. Our data indicate that DCs can generate CD25+ CD4+ T cells that suppress autoimmune disease in vivo. This might be harnessed as a new avenue for immunotherapy, especially because CD25+ CD4+ regulatory cells responsive to a single autoantigen can inhibit diabetes mediated by reactivity to multiple antigens.