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Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line

Nando Dulal Das1, Kyoung Hwa Jung, Mi Ran Choi

  • 1Division of Molecular and Life Science, Hanyang University, Ansan, South Korea.

Cell Biochemistry and Function
|January 19, 2012
PubMed

Insights

JMJD3 knockdown in human monocytic cells impacts inflammatory gene expression by altering histone modifications. This epigenetic regulator, nuclear factor-kappa B (NF-κB), influences key inflammatory and signalling pathways.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cell Biology

Background:

  • JMJD3 is a histone demethylase induced by NF-κB, crucial for activating genes by removing repressive H3K27me3 marks.
  • NF-κB is a key transcription factor involved in inflammatory and immune responses.

Purpose of the Study:

  • To identify genes regulated by JMJD3 in human monocytic cells (THP-1).
  • To investigate the role of JMJD3 in inflammatory signalling pathways.
  • To elucidate the epigenetic mechanisms linking NF-κB and JMJD3.

Main Methods:

  • Stable knockdown of JMJD3 in THP-1 cells.
  • Global gene expression analysis using NimbleGen whole genome arrays.
  • Ingenuity Pathway Analysis (IPA) for data interpretation.
  • Chromatin immunoprecipitation (ChIP) to assess histone modifications.

Main Results:

  • JMJD3 knockdown significantly altered gene expression, particularly affecting inflammatory signalling pathways.
  • JMJD3 attenuation down-regulated key genes in NF-κB, chemokine, and CD40 signalling.
  • JMJD3 knockdown led to increased H3K27me3 at promoters of NF-κB-regulated inflammatory genes, inhibiting their expression.
  • IPA identified novel JMJD3 targets and highlighted the connection between NF-κB and JMJD3.

Conclusions:

  • JMJD3 plays a critical role in regulating inflammatory gene expression in monocytic cells.
  • Epigenetic mechanisms involving JMJD3 and H3K27me3 are central to NF-κB-mediated inflammatory responses.
  • This study identifies novel targets and pathways regulated by JMJD3, offering insights into epigenetic regulation of inflammation.

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