The transcription factor STAT6 mediates direct repression of inflammatory enhancers and limits activation of alternatively polarized macrophages

The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-κB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1β production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli

Identification of a Novel “Chromosome Scaffold” Protein That Associates with Tec Elements Undergoing En Masse Elimination in Euplotes crassus

During macronuclear development in the ciliate Euplotes crassus, the highly repetitive, transposon-like Tec elements possess an unusual chromatin structure. We observed that the Tec element chromatin is highly resistant to salt extraction and behaves like a nuclear matrix/chromosome scaffold-associated structure. Standard matrix/scaffold extraction procedures identified two major proteins: 1) an ∼140-kDa protein that seems to be topoisomerase II based on its reactivity with anti-topoisomerase II antibodies, and 2) an 85-kDa protein that we further purified by acid extraction and have shown to be a novel protein by sequence analysis of its gene. The 85-kDa protein (p85) is a developmental stage-specific protein and is located exclusively in the developing macronucleus. Immunolocalization studies of p85 show that it colocalizes with topoisomerase II in chromatin. In addition, in situ hybridization combined with immunofluorescence localization of the proteins indicates that 100% of the Tec elements colocalize with 70% of the p85, whereas no significant colocalization with a total macronuclear sequence-specific probe is observed. p85 is the first developmental stage-specific protein identified as being specifically associated with sequences undergoing elimination in E. crassus

25 Years of Self-Organized Criticality: Solar and Astrophysics

Shortly after the seminal paper “Self-Organized Criticality: An explanation of 1/fnoise” by Bak et al. (1987), the idea has been applied to solar physics, in “Avalanches and the Distribution of Solar Flares” by Lu and Hamilton (1991). In the following years, an inspiring cross-fertilization from complexity theory to solar and astrophysics took place, where the SOC concept was initially applied to solar flares, stellar flares, and magnetospheric substorms, and later extended to the radiation belt, the heliosphere, lunar craters, the asteroid belt, the Saturn ring, pulsar glitches, soft X-ray repeaters, blazars, black-hole objects, cosmic rays, and boson clouds. The application of SOC concepts has been performed by numerical cellular automaton simulations, by analytical calculations of statistical (powerlaw-like) distributions based on physical scaling laws, and by observational tests of theoretically predicted size distributions and waiting time distributions. Attempts have been undertaken to import physical models into the numerical SOC toy models, such as the discretization of magneto-hydrodynamics (MHD) processes. The novel applications stimulated also vigorous debates about the discrimination between SOC models, SOC-like, and non-SOC processes, such as phase transitions, turbulence, random-walk diffusion, percolation, branching processes, network theory, chaos theory, fractality, multi-scale, and other complexity phenomena. We review SOC studies from the last 25 years and highlight new trends, open questions, and future challenges, as discussed during two recent ISSI workshops on this theme.Fil: Aschwanden, Markus J.. Lockheed Martin Corporation; Estados UnidosFil: Crosby, Norma B.. Belgian Institute For Space Aeronomy; BélgicaFil: Dimitropoulou, Michaila. University Of Athens; GreciaFil: Georgoulis, Manolis K.. Academy Of Athens; GreciaFil: Hergarten, Stefan. Universitat Freiburg Im Breisgau; AlemaniaFil: McAteer, James. University Of New Mexico; Estados UnidosFil: Milovanov, Alexander V.. Max Planck Institute For The Physics Of Complex Systems; Alemania. Russian Academy Of Sciences. Space Research Institute; Rusia. Enea Centro Ricerche Frascati; ItaliaFil: Mineshige, Shin. Kyoto University; JapónFil: Morales, Laura Fernanda. Canadian Space Agency; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nishizuka, Naoto. Japan National Institute Of Information And Communications Technology; JapónFil: Pruessner, Gunnar. Imperial College London; Reino UnidoFil: Sanchez, Raul. Universidad Carlos Iii de Madrid. Instituto de Salud; EspañaFil: Sharma, A. Surja. University Of Maryland; Estados UnidosFil: Strugarek, Antoine. University Of Montreal; CanadáFil: Uritsky, Vadim. Nasa Goddard Space Flight Center; Estados Unido