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Gene networking and canonical pathway analysis in a JMJD3 knockdown human monocytic cell line
Author(s) -
Das Nando Dulal,
Jung Kyoung Hwa,
Choi Mi Ran,
Chai Young Gyu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb63
Subject(s) - gene knockdown , demethylase , biology , gene , histone , small hairpin rna , gene expression , epigenetics , thp1 cell line , signal transduction , regulation of gene expression , cell culture , microbiology and biotechnology , genetics
JMJD3, a JmjC family histone demethylase, can be induced by the transcription factor NF‐kB in response to various stimuli. JMJD3 is crucial for erasing H3K27me3, a histone modification associated with transcriptional repression, and is responsible for the activation of a diverse set of genes. The objectives of this study were to identify the genes in THP‐1 human monocytic cells that are significantly affected by the knockdown of JMJD3, particularly in expression levels and in downstream effects on signaling pathways. THP‐1 cells were subjected to lentiviral JMJD3 shRNA transduction followed by analysis of gene expression by qRT‐PCR. Global gene expression levels were detected in JMJD3 knockdown (kd) THP‐1 human monocytic cells and in TNF‐stimulated JMJD3‐kd THP‐1 cells using a 44‐k human whole genome array. Finally, datasets were analyzed using Ingenuity pathway analysis (IPA) software. IPA analysis reveals that JMJD3 attenuation down‐regulates various key genes in NF‐kB, chemokine and CD40 signaling and mostly affects inflammatory disease response molecules. Moreover, this study significantly highlights the connection of NF‐kB with JMJD3, which suggests an epigenetic regulation of the inflammatory genes. Funded by NRF‐2009‐0077023; Korea.