Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
| Autor: | Alan J. Mears, Ilya Ioshikhes, David J. Picketts, Romit Majumder, Valerie A. Wallace, Rashmi Kothary, Danton Ivanochko, Erin A. Bassett, Juraj Kokavec, Matías Alvarez-Saavedra, Arthur I. Skoultchi, Matthew A. M. Todd, Keqin Yan, Pamela S. Lagali, Michael S. Huh, Tomas Stopka, Nicholas Tokarew, Edupuganti V.S. Raghu Ram, Eran Meshorer, Doo Yang, Emile Hashem, Yves De Repentigny, Chelsea P. Corcoran |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cerebellum Indoles Chromosomal Proteins Non-Histone General Physics and Astronomy Histones Mice Purkinje Cells Neural Stem Cells Image Processing Computer-Assisted Morphogenesis Tolonium Chloride In Situ Hybridization Adenosine Triphosphatases Multidisciplinary biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Immunohistochemistry Chromatin Cell biology Histone medicine.anatomical_structure Female Chromatin Immunoprecipitation Blotting Western Mice Transgenic Real-Time Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Chromatin remodeling Fluorescence Article Histone H1 Microscopy Electron Transmission medicine In Situ Nick-End Labeling Animals Homeodomain Proteins Analysis of Variance Galactosides General Chemistry Chromatin Assembly and Disassembly Microarray Analysis Embryonic stem cell nervous system Bromodeoxyuridine Rotarod Performance Test biology.protein Chromatin immunoprecipitation |
| Zdroj: | Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The chromatin remodelling proteins Snf2h and Snf2l regulate nucleosome spacing. Here, the authors show that Snf2h ablation impairs chromatin organization of neuronal lineages during mouse embryonic and post-natal cerebellar development. |
| Databáze: | OpenAIRE |
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