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

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 Todd, Chelsea P. Corcoran, Erin A. Bassett, Nicholas J A Tokarew, Juraj Kokavec, Romit Majumder, Ilya Ioshikhes, Valerie A. Wallace, Rashmi Kothary, Eran MeshorerTomas Stopka, Arthur I. Skoultchi, David J. Picketts

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Article number4181
JournalNature Communications
Volume5
DOIs
StatePublished - Jun 20 2014

Fingerprint

chromatin
Morphogenesis
Histones
Chromatin
gene expression
Gene expression
mice
Gene Expression
Neuronal Plasticity
Motor Skills
Chromatin Assembly and Disassembly
cerebellum
Nucleosomes
Purkinje Cells
Fluidity
adenosine triphosphate
Cerebellum
Ablation
neurons
death

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Alvarez-Saavedra, M., De Repentigny, Y., Lagali, P. S., Raghu Ram, E. V. S., Yan, K., Hashem, E., ... Picketts, D. J. (2014). Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation. Nature Communications, 5, [4181]. https://doi.org/10.1038/ncomms5181

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.

In: Nature Communications, Vol. 5, 4181, 20.06.2014.

Research output: Contribution to journalArticle

Alvarez-Saavedra, M, De Repentigny, Y, Lagali, PS, Raghu Ram, EVS, Yan, K, Hashem, E, Ivanochko, D, Huh, MS, Yang, D, Mears, AJ, Todd, MAM, Corcoran, CP, Bassett, EA, Tokarew, NJA, Kokavec, J, Majumder, R, Ioshikhes, I, Wallace, VA, Kothary, R, Meshorer, E, Stopka, T, Skoultchi, AI & Picketts, DJ 2014, 'Snf2h-mediated chromatin organization and histone H1 dynamics govern cerebellar morphogenesis and neural maturation', Nature Communications, vol. 5, 4181. https://doi.org/10.1038/ncomms5181
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. In: Nature Communications. 2014 ; Vol. 5.
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