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

M. Alvarez-Saavedra, Y. De Repentigny, PS. Lagali, EV. Raghu Ram, K. Yan, E. Hashem, D. Ivanochko, MS. Huh, D. Yang, AJ. Mears, MA. Todd, CP. Corcoran, EA. Bassett, NJ. Tokarew, J. Kokavec, R. Majumder, I. Ioshikhes, VA. Wallace, R. Kothary, E....

. 2014 ; 5 (-) : 4181. [pub] 20140620

Language English Country England, Great Britain

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15031992

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.

] 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

] 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

] 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

] 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

] 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

Department of Biochemistry Microbiology and Immunology University of Ottawa Ottawa Ontario Canada K1H 8M5

Department of Cell Biology Albert Einstein College of Medicine Bronx New York 10461 USA

Department of Genetics The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem 91904 Israel

Institute of Pathologic Physiology 1st Faculty of Medicine Charles University Prague Prague 12853 Czech Republic

Regenerative Medicine Program Ottawa Hospital Research Institute Ottawa Ontario Canada K1H 8L6

Vision Program Ottawa Hospital Research Institute Ottawa Ontario Canada K1H 8L6

References provided by Crossref.org

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