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

Author

Listed:
  • Matías Alvarez-Saavedra

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    University of Ottawa)

  • Yves De Repentigny

    (Regenerative Medicine Program, Ottawa Hospital Research Institute)

  • Pamela S. Lagali

    (Regenerative Medicine Program, Ottawa Hospital Research Institute)

  • Edupuganti V. S. Raghu Ram

    (The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem)

  • Keqin Yan

    (Regenerative Medicine Program, Ottawa Hospital Research Institute)

  • Emile Hashem

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    University of Ottawa)

  • Danton Ivanochko

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    Microbiology and Immunology, University of Ottawa)

  • Michael S. Huh

    (Regenerative Medicine Program, Ottawa Hospital Research Institute)

  • Doo Yang

    (Microbiology and Immunology, University of Ottawa
    Institute of Systems Biology, University of Ottawa)

  • Alan J. Mears

    (Vision Program, Ottawa Hospital Research Institute)

  • Matthew A. M. Todd

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    Microbiology and Immunology, University of Ottawa)

  • Chelsea P. Corcoran

    (Regenerative Medicine Program, Ottawa Hospital Research Institute)

  • Erin A. Bassett

    (Microbiology and Immunology, University of Ottawa)

  • Nicholas J. A. Tokarew

    (Microbiology and Immunology, University of Ottawa)

  • Juraj Kokavec

    (Institute of Pathologic Physiology, First Faculty of Medicine, Charles University in Prague)

  • Romit Majumder

    (Albert Einstein College of Medicine)

  • Ilya Ioshikhes

    (Microbiology and Immunology, University of Ottawa
    Institute of Systems Biology, University of Ottawa)

  • Valerie A. Wallace

    (Microbiology and Immunology, University of Ottawa
    Vision Program, Ottawa Hospital Research Institute)

  • Rashmi Kothary

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    University of Ottawa)

  • Eran Meshorer

    (The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem)

  • Tomas Stopka

    (Institute of Pathologic Physiology, First Faculty of Medicine, Charles University in Prague)

  • Arthur I. Skoultchi

    (Albert Einstein College of Medicine)

  • David J. Picketts

    (Regenerative Medicine Program, Ottawa Hospital Research Institute
    University of Ottawa
    Microbiology and Immunology, University of Ottawa)

Abstract

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.

Suggested Citation

  • Matías Alvarez-Saavedra & Yves De Repentigny & Pamela S. Lagali & Edupuganti V. S. Raghu Ram & Keqin Yan & Emile Hashem & Danton Ivanochko & Michael S. Huh & Doo Yang & Alan J. Mears & Matthew A. M. T, 2014. "Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation," Nature Communications, Nature, vol. 5(1), pages 1-18, September.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5181
    DOI: 10.1038/ncomms5181
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