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Snf2h-mediated chromatin organization and histone H1 dynamics govern 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...

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Autores principales: Alvarez-Saavedra, Matías, De Repentigny, Yves, Lagali, Pamela S., Raghu Ram, Edupuganti V. S., Yan, Keqin, Hashem, Emile, Ivanochko, Danton, Huh, Michael S., Yang, Doo, Mears, Alan J., Todd, Matthew A. M., Corcoran, Chelsea P., Bassett, Erin A., Tokarew, Nicholas J. A., Kokavec, Juraj, Majumder, Romit, Ioshikhes, Ilya, Wallace, Valerie A., Kothary, Rashmi, Meshorer, Eran, Stopka, Tomas, Skoultchi, Arthur I., Picketts, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083431/
https://www.ncbi.nlm.nih.gov/pubmed/24946904
http://dx.doi.org/10.1038/ncomms5181
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author Alvarez-Saavedra, Matías
De Repentigny, Yves
Lagali, Pamela S.
Raghu Ram, Edupuganti V. S.
Yan, Keqin
Hashem, Emile
Ivanochko, Danton
Huh, Michael S.
Yang, Doo
Mears, Alan J.
Todd, Matthew A. M.
Corcoran, Chelsea P.
Bassett, Erin A.
Tokarew, Nicholas J. A.
Kokavec, Juraj
Majumder, Romit
Ioshikhes, Ilya
Wallace, Valerie A.
Kothary, Rashmi
Meshorer, Eran
Stopka, Tomas
Skoultchi, Arthur I.
Picketts, David J.
author_facet Alvarez-Saavedra, Matías
De Repentigny, Yves
Lagali, Pamela S.
Raghu Ram, Edupuganti V. S.
Yan, Keqin
Hashem, Emile
Ivanochko, Danton
Huh, Michael S.
Yang, Doo
Mears, Alan J.
Todd, Matthew A. M.
Corcoran, Chelsea P.
Bassett, Erin A.
Tokarew, Nicholas J. A.
Kokavec, Juraj
Majumder, Romit
Ioshikhes, Ilya
Wallace, Valerie A.
Kothary, Rashmi
Meshorer, Eran
Stopka, Tomas
Skoultchi, Arthur I.
Picketts, David J.
author_sort Alvarez-Saavedra, Matías
collection PubMed
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.
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spelling pubmed-40834312014-07-09 Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation Alvarez-Saavedra, Matías De Repentigny, Yves Lagali, Pamela S. Raghu Ram, Edupuganti V. S. Yan, Keqin Hashem, Emile Ivanochko, Danton Huh, Michael S. Yang, Doo Mears, Alan J. Todd, Matthew A. M. Corcoran, Chelsea P. Bassett, Erin A. Tokarew, Nicholas J. A. Kokavec, Juraj Majumder, Romit Ioshikhes, Ilya Wallace, Valerie A. Kothary, Rashmi Meshorer, Eran Stopka, Tomas Skoultchi, Arthur I. Picketts, David J. Nat Commun Article 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. Nature Pub. Group 2014-06-20 /pmc/articles/PMC4083431/ /pubmed/24946904 http://dx.doi.org/10.1038/ncomms5181 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Article
Alvarez-Saavedra, Matías
De Repentigny, Yves
Lagali, Pamela S.
Raghu Ram, Edupuganti V. S.
Yan, Keqin
Hashem, Emile
Ivanochko, Danton
Huh, Michael S.
Yang, Doo
Mears, Alan J.
Todd, Matthew A. M.
Corcoran, Chelsea P.
Bassett, Erin A.
Tokarew, Nicholas J. A.
Kokavec, Juraj
Majumder, Romit
Ioshikhes, Ilya
Wallace, Valerie A.
Kothary, Rashmi
Meshorer, Eran
Stopka, Tomas
Skoultchi, Arthur I.
Picketts, David J.
Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title_full Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title_fullStr Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title_full_unstemmed Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title_short Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation
title_sort snf2h-mediated chromatin organization and histone h1 dynamics govern cerebellar morphogenesis and neural maturation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083431/
https://www.ncbi.nlm.nih.gov/pubmed/24946904
http://dx.doi.org/10.1038/ncomms5181
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