The H3K27 Demethylase JMJD3 Is Required for Maintenance of the Embryonic Respiratory Neuronal Network, Neonatal Breathing, and Survival

Thomas Burgold, Nicolas Voituron, Marieta Caganova, Prem Prakash Tripathi, Clement Menuet, Betsabeh Khoramian Tusi, Fabio Spreafico, Michelle Bévengut, Christian Gestreau, Serena Buontempo, Antonio Simeone, Laurens Kruidenier, Gioacchino Natoli, Stefano Casola, Gérard Hilaire, Giuseppe Testa

Research output: Contribution to journalArticle

Abstract

JMJD3 (KDM6B) antagonizes Polycomb silencing by demethylating lysine 27 on histone H3. The interplay of methyltransferases and demethylases at this residue is thought to underlie critical cell fate transitions, and the dynamics of H3K27me3 during neurogenesis posited for JMJD3 a critical role in the acquisition of neural fate. Despite evidence of its involvement in early neural commitment, however, its role in the emergence and maturation of the mammalian CNS remains unknown. Here, we inactivated Jmjd3 in the mouse and found that its loss causes perinatal lethality with the complete and selective disruption of the pre-Bötzinger complex (PBC), the pacemaker of the respiratory rhythm generator. Through genetic and electrophysiological approaches, we show that the enzymatic activity of JMJD3 is selectively required for the maintenance of the PBC and controls critical regulators of PBC activity, uncovering an unanticipated role of this enzyme in the late structuring and function of neuronal networks.

Original languageEnglish
Pages (from-to)1244-1258
Number of pages15
JournalCell Reports
Volume2
Issue number5
DOIs
Publication statusPublished - Nov 29 2012

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Burgold, T., Voituron, N., Caganova, M., Tripathi, P. P., Menuet, C., Tusi, B. K., Spreafico, F., Bévengut, M., Gestreau, C., Buontempo, S., Simeone, A., Kruidenier, L., Natoli, G., Casola, S., Hilaire, G., & Testa, G. (2012). The H3K27 Demethylase JMJD3 Is Required for Maintenance of the Embryonic Respiratory Neuronal Network, Neonatal Breathing, and Survival. Cell Reports, 2(5), 1244-1258. https://doi.org/10.1016/j.celrep.2012.09.013