Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals
Autore:
Fan, GP; Beard, C; Chen, RZ; Csankovszki, G; Sun, Y; Siniaia, M; Biniszkiewicz, D; Bates, B; Lee, PP; Kuhn, R; Trumpp, A; Poon, CS; Wilson, CB; Jaenisch, R;
Indirizzi:
Whitehead Inst Biomed Res, Cambridge, MA 02142 USA Whitehead Inst Biomed Res Cambridge MA USA 02142 Cambridge, MA 02142 USA MIT, Dept Biol, Cambridge, MA 02142 USA MIT Cambridge MA USA 02142MIT, Dept Biol, Cambridge, MA 02142 USA Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol,Div Neurosci, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 eurol,Div Neurosci, Boston, MA 02115 USA MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139 iv Hlth Sci & Technol, Cambridge, MA 02139 USA Univ Washington, Dept Immunol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 Dept Immunol, Seattle, WA 98195 USA Univ Washington, Dept Pediat, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 , Dept Pediat, Seattle, WA 98195 USA Univ Calif San Francisco, GW Hooper Fdn, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Cologne, Dept Genet, Cologne, Germany Univ Cologne Cologne GermanyUniv Cologne, Dept Genet, Cologne, Germany
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 3, volume: 21, anno: 2001,
pagine: 788 - 797
SICI:
0270-6474(20010201)21:3<788:DHPTFA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHYLTRANSFERASE GENE; RETT-SYNDROME; CYTOSINE-5 METHYLTRANSFERASES; CEREBRAL-CORTEX; METHYLATION; CELLS; EXPRESSION; GROWTH; DIFFERENTIATION; PATTERNS;
Keywords:
DNA methylation; Dnmt1; demethylation; neural development; cre/loxP system; respiration; epigenetic mechanism; gene regulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Jaenisch, R Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA Whitehead Inst Biomed Res 9 Cambridge Ctr Cambridge MA USA 02142
Citazione:
G.P. Fan et al., "DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals", J NEUROSC, 21(3), 2001, pp. 788-797

Abstract

DNA methyltransferase 1 (Dnmt1), the maintenance enzyme for DNA cytosine methylation, is expressed at high levels in the CNS during embryogenesis andafter birth. Because embryos deficient for Dnmt1 die at gastrulation, the role of Dnmt1 in the development and function of the nervous system could not be studied by using this mutation. We therefore used the cre/loxP systemto produce conditional mutants that lack Dnmt1 in neuroblasts of embryonicday 12 embryos or in postmitotic neurons of the postnatal animal. Conditional deletion of the Dnmt1 gene resulted in rapid depletion of Dnmt1 proteins, indicating that the enzyme in postmitotic neurons turns over quickly. Dnmt1 deficiency in postmitotic neurons neither affected levels of global DNAmethylation nor influenced cell survival during postnatal life. In contrast, Dnmt1 deficiency in mitotic CNS precursor cells resulted in DNA hypomethylation in daughter cells. Whereas mutant embryos carrying 95% hypomethylated cells in the brain died immediately after birth because of respiratory distress, mosaic animals with 30% hypomethylated CNS cells were viable into adulthood. However, these mutant cells were eliminated quickly from the brain within 3 weeks of postnatal life. Thus, hypomethylated CNS neurons were impaired functionally and were selected against at postnatal stages.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 10:28:11