About: Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation     Goto   Sponge   Distinct   Permalink

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Description
  • 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.
  • 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. (en)
Title
  • Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
  • Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation (en)
skos:prefLabel
  • Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
  • Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation (en)
skos:notation
  • RIV/00216208:11110/14:10282396!RIV15-MSM-11110___
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • I, P(GAP305/12/1033)
http://linked.open...iv/cisloPeriodika
  • JUN
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  • 45529
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11110/14:10282396
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • target genes; living cells; mouse development; differential expression; linker histone; sonic hedgehog; gene-expression; remodeling complex; in-vivo; embryonic stem-cells (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [4B5E57065715]
http://linked.open...i/riv/nazevZdroje
  • Nature Communications
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 5
http://linked.open...iv/tvurceVysledku
  • Stopka, Tomáš
  • Kokavec, Juraj
  • Alvarez-Saavedra, Matias
  • Bassett, Erin A.
  • Corcoran, Chelsea P.
  • De Repentigny, Yves
  • Hashem, Emile
  • Huh, Michael S.
  • Ioshikhes, Ilya
  • Ivanochko, Danton
  • Kothary, Rashmi
  • Lagali, Pamela S.
  • Majumder, Romit
  • Mears, Alan J.
  • Meshorer, Eran
  • Picketts, David J.
  • Ram, Edupuganti V. S. Raghu
  • Skoultchi, Arthur I.
  • Todd, Matthew A. M.
  • Tokarew, Nicholas J. A.
  • Wallace, Valerie A.
  • Yan, Keqin
  • Yang, Doo
http://linked.open...ain/vavai/riv/wos
  • 000338838700006
issn
  • 2041-1723
number of pages
http://bibframe.org/vocab/doi
  • 10.1038/ncomms5181
http://localhost/t...ganizacniJednotka
  • 11110
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