KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity

Wellcome Trust [102349/Z/13/Z to A.H.T., 099677/Z/12/Z to H.W.K., 098024/Z/11/Z, 209400/Z/17/Z to R.J.K.]; Lister Institute of Preventive Medicine; European Research Council [681440]; Japan Agency for Medical Research and Development, AMEDCREST Programme. Funding for open access charge: Wellcome Trus

TOPORS (topoisomerase I binding, arginine/serine-rich)

Review on TOPORS (topoisomerase I binding, arginine/serine-rich), with data on DNA, on the protein encoded, and where the gene is implicated

Self-Diffusion of a Polymer Chain in a Melt

Self-diffusion of a polymer chain in a melt is studied by Monte Carlo simulations of the bond fluctuation model, where only the excluded volume interaction is taken into account. Polymer chains, each of which consists of $N$ segments, are located on an $L \times L \times L$ simple cubic lattice under periodic boundary conditions, where each segment occupies $2 \times 2 \times 2$ unit cells. The results for $N=32, 48, 64, 96, 128, 192, 256, 384$ and 512 at the volume fraction $\phi \simeq 0.5$ are reported, where $L = 128$ for $N \leq 256$ and L=192 for $N \geq 384$. The $N$-dependence of the self-diffusion constant $D$ is examined. Here, $D$ is estimated from the mean square displacements of the center of mass of a single polymer chain at the times larger than the longest relaxation time. From the data for $N = 256$, 384 and 512, the apparent exponent $x_{\rm d}$, which describes the apparent power law dependence of $D$ on $N$ as $D \propto N^{- x_{\rm d}}$, is estimated as $x_{\rm d} \simeq 2.4$. The ratio $D \tau /$ seems to be a constant for $N = 192, 256, 384$ and 512, where $\tau$ and $$ denote the longest relaxation time and the mean square end-to-end distance, respectively.Comment: 4 pages, 3 figures, submitted to J. Phys. Soc. Jp

EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment

Central nervous system (CNS) axons lose their intrinsic ability to regenerate upon maturity, whereas peripheral nervous system (PNS) axons do not. A key difference between these neuronal types is their ability to transport integrins into axons. Integrins can mediate PNS regeneration, but are excluded from adult CNS axons along with their Rab11 carriers. We reasoned that exclusion of the contents of Rab11 vesicles including integrins might contribute to the intrinsic inability of CNS neurons to regenerate, and investigated this by performing laser axotomy. We identify a novel regulator of selective axon transport and regeneration, the ARF6 guanine-nucleotide-exchange factor (GEF) EFA6 (also known as PSD). EFA6 exerts its effects from a location within the axon initial segment (AIS). EFA6 does not localise at the AIS in dorsal root ganglion (DRG) axons, and in these neurons, ARF6 activation is counteracted by an ARF GTPase-activating protein (GAP), which is absent from the CNS, ACAP1. Depleting EFA6 from cortical neurons permits endosomal integrin transport and enhances regeneration, whereas overexpressing EFA6 prevents DRG regeneration. Our results demonstrate that ARF6 is an intrinsic regulator of regenerative capacity, implicating EFA6 as a focal molecule linking the AIS, signalling and transport.The study was funded by grants from the Christopher and Dana Reeve Foundation, the Medical Research Council, the ERC advanced grant ECMneuro, the International Spinal Research Trust, Glaxo Smith Kline International Scholarship, Honjo International Scholarship, Bristol-Myers Squibb Graduate Studentship and the NIHR Cambridge Biomedical Research Centre

Average Structures of a Single Knotted Ring Polymer

Two types of average structures of a single knotted ring polymer are studied by Brownian dynamics simulations. For a ring polymer with N segments, its structure is represented by a 3N -dimensional conformation vector consisting of the Cartesian coordinates of the segment positions relative to the center of mass of the ring polymer. The average structure is given by the average conformation vector, which is self-consistently defined as the average of the conformation vectors obtained from a simulation each of which is rotated to minimize its distance from the average conformation vector. From each conformation vector sampled in a simulation, 2N conformation vectors are generated by changing the numbering of the segments. Among the 2N conformation vectors, the one closest to the average conformation vector is used for one type of the average structure. The other type of the averages structure uses all the conformation vectors generated from those sampled in a simulation. In thecase of the former average structure, the knotted part of the average structure is delocalized for small N and becomes localized as N is increased. In the case of the latter average structure, the average structure changes from a double loop structure for small N to a single loop structure for large N, which indicates the localization-delocalization transition of the knotted part.Comment: 15 pages, 19 figures, uses jpsj2.cl

Maintenance of Undifferentiated State and Self-Renewal of Embryonic Neural Stem Cells by Polycomb Protein Ring1B

12 pages, 7 figures.-- PMID: 19544461 [PubMed].-- Printed version published Jul 2009.Supporting information (Suppl. figures S1-S9, tables S1-S2) available at: http://www3.interscience.wiley.com/journal/122302104/suppinfoCell lineages generated during development and tissue maintenance are derived from self-renewing stem cells by differentiation of their committed progeny. Recent studies suggest that epigenetic mechanisms, and in particular the Polycomb group (PcG) of genes, play important roles in controlling stem cell self-renewal. Here, we address PcG regulation of stem cell self-renewal and differentiation through inactivation of Ring1B, a histone H2A E3 monoubiquitin ligase, in embryonic neural stem cells (NSCs) from the olfactory bulb of a conditional mouse mutant line. We show that neural stem/progenitor cell proliferation in vivo and in neurosphere assays is impaired, lacking Ring1B, and their self-renewal and multipotential abilities, assessed as sphere formation and differentiation from single cells, are severely affected. We also observed unscheduled neuronal, but not glial, differentiation of mutant stem/progenitor cells under proliferating conditions, an alteration enhanced in cells also lacking Ring1A, the Ring1B paralog, some of which turned into morphologically identifiable neurons. mRNA analysis of mutant cells showed upregulation of some neuronal differentiation-related transcription factors and the cell proliferation inhibitor Cdkn1a/p21, as well as downregulation of effectors of the Notch signaling pathway, a known inhibitor of neuronal differentiation of stem/progenitor cells. In addition, differentiation studies of Ring1B-deficient progenitors showed decreased oligodendrocyte formation in vitro and enhanced neurogenesis and reduced gliogenesis in vivo. These data suggest a role for Ring1B in maintenance of the undifferentiated state of embryonic neural stem/progenitor cells. They also suggest that Ring1B may modulate the differentiation potential of NSCs to neurons and glia.M.R-T. and H. M-G. were recipients of FPU and FPI fellowships, from the Ministerio de Educacion y Ciencia and Comunidad de Madrid, respectively. This work was supported by grants SAF2007-65957-C02-01 (M.V.), the Onco-Cycle program from the Comunidad de Madrid (M.V.), SAF2004-05798, and CIBERNED CB06/05/0065 from Instituto de Salud Carlos III (C.V-A.).Peer reviewe