Nucleocytoplasmic translocation of HDAC9 regulates gene expression and dendritic growth in developing cortical neurons.
Transcriptional regulation of gene expression is thought to play a pivotal role in activity-dependent neuronal differentiation and circuit formation. Here, we investigated the role of histone deacetylase 9 (HDAC9), which regulates transcription by histone modification, in the development of neocortical neurons. The translocation of HDAC9 from nucleus to cytoplasm was induced by an increase of spontaneous firing activity in cultured mouse cortical neurons. This nucleocytoplasmic translocation was also observed in postnatal development in vivo. The translocation-induced gene expression and cellular morphology was further examined by introducing an HDAC9 mutant that disrupts the nucleocytoplasmic translocation. Expression of c-fos, an immediately-early gene, was suppressed in the mutant-transfected cells regardless of neural activity. Moreover, the introduction of the mutant decreased the total length of dendritic branches, whereas knockdown of HDAC9 promoted dendritic growth. These findings indicate that chromatin remodeling with nucleocytoplasmic translocation of HDAC9 regulates activity-dependent gene expression and dendritic growth in developing cortical neurons.
Sugo
Noriyuki
N
Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan. sugo@fbs.osaka-u.ac.jp
Oshiro
Hiroaki
H
Takemura
Mitsuhiro
M
Kobayashi
Toshiaki
T
Kohno
Yusuke
Y
Uesaka
Naofumi
N
Song
Wen-Jie
WJ
Yamamoto
Nobuhiko
N
D000200:Action Potentials; D021581:Active Transport, Cell Nucleus; D000818:Animals; D049108:Cell Enlargement; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; C552726:HDAC9 protein, rat; C486545:Hdac9 protein, mouse; D006655:Histone Deacetylases