Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation.

Autor:	Alvarez-Saavedra M; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., De Repentigny Y; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Lagali PS; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Raghu Ram EV; Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel., Yan K; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Hashem E; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Ivanochko D; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Huh MS; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Yang D; 1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 [2] Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Mears AJ; Vision Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Todd MA; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Corcoran CP; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Bassett EA; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Tokarew NJ; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Kokavec J; Institute of Pathologic Physiology, First Faculty of Medicine, Charles University in Prague, Prague 12853, Czech Republic., Majumder R; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA., Ioshikhes I; 1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 [2] Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Wallace VA; 1] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 [2] Vision Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6., Kothary R; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5., Meshorer E; Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel., Stopka T; Institute of Pathologic Physiology, First Faculty of Medicine, Charles University in Prague, Prague 12853, Czech Republic., Skoultchi AI; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA., Picketts DJ; 1] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada K1H 8L6 [2] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5 [3] Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2014 Jun 20; Vol. 5, pp. 4181. Date of Electronic Publication: 2014 Jun 20.
DOI:	10.1038/ncomms5181
Abstrakt:	Chromatin compaction mediates progenitor to post-mitotic cell transitions and modulates gene expression programs, yet the mechanisms are poorly defined. Snf2h and Snf2l are ATP-dependent chromatin remodelling proteins that assemble, reposition and space nucleosomes, and are robustly expressed in the brain. Here we show that mice conditionally inactivated for Snf2h in neural progenitors have reduced levels of histone H1 and H2A variants that compromise chromatin fluidity and transcriptional programs within the developing cerebellum. Disorganized chromatin limits Purkinje and granule neuron progenitor expansion, resulting in abnormal post-natal foliation, while deregulated transcriptional programs contribute to altered neural maturation, motor dysfunction and death. However, mice survive to young adulthood, in part from Snf2l compensation that restores Engrailed-1 expression. Similarly, Purkinje-specific Snf2h ablation affects chromatin ultrastructure and dendritic arborization, but alters cognitive skills rather than motor control. Our studies reveal that Snf2h controls chromatin organization and histone H1 dynamics for the establishment of gene expression programs underlying cerebellar morphogenesis and neural maturation.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu