Histone demethylase Jmjd3 regulates osteoblast apoptosis through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim

Di Yang, Hirohiko Okamura, Jumpei Teramachi, Tatsuji Haneji

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Posttranslational modifications including histone methylation regulate gene transcription through directly affecting the structure of chromatin. Trimethylation of histone H3K27 (H3K27me3) contributes to gene silencing and the histone demethylase Jumonji domain-containing 3 (Jmjd3) specifically removes the methylation of H3K27me3, followed by the activation of gene expression. In the present study, we explored the roles of Jmjd3 in regulating osteoblast apoptosis. Knockdown of Jmjd3 promoted osteoblast apoptosis induced by serum deprivation with decreased mitochondrial membrane potential and increased levels of caspase-3 activation, PARP cleavage, and DNA fragmentation. B cell lymphoma-2 (Bcl-2), an anti-apoptotic protein, was down-regulated by knockdown of Jmjd3 through retaining H3K27me3 on its promoter region. Knockdown of Jmjd3 increased the pro-apoptotic activity of Bim through inhibiting ERK-dependent phosphorylation of Bim. Protein kinase D1 (PKD1), which stimulates ERK phosphorylation, decreased in the Jmjd3-knockdown cells and introduction of PKD1 relieved osteoblast apoptosis in the Jmjd3-knockdown cells through increasing ERK-regulated Bim phosphorylation. These results suggest that Jmjd3 regulates osteoblast apoptosis through targeting Bcl-2 expression and Bim phosphorylation.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1863
Issue number4
DOIs
Publication statusPublished - Apr 1 2016
Externally publishedYes

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Jumonji Domain-Containing Histone Demethylases
Apoptosis Regulatory Proteins
B-Cell Lymphoma
Osteoblasts
Phosphorylation
Apoptosis
Histones
Protein Kinases
Methylation
Mitochondrial Membrane Potential
Gene Silencing
DNA Fragmentation
Post Translational Protein Processing
Genetic Promoter Regions
Caspase 3
Chromatin
Gene Expression
IgA receptor
Serum
Genes

Keywords

  • Bcl-2
  • Bim
  • Histone demethylation
  • Jmjd3
  • Osteoblast apoptosis
  • Protein kinase D1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Histone demethylase Jmjd3 regulates osteoblast apoptosis through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim. / Yang, Di; Okamura, Hirohiko; Teramachi, Jumpei; Haneji, Tatsuji.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1863, No. 4, 01.04.2016, p. 650-659.

Research output: Contribution to journalArticle

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