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Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line
Author(s) -
Das Nando Dulal,
Jung Kyoung Hwa,
Choi Mi Ran,
Yoon Hyun Soo,
Kim Seung Hyun,
Chai Young Gyu
Publication year - 2012
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1839
Subject(s) - gene knockdown , chromatin immunoprecipitation , demethylase , biology , transcription factor , histone , thp1 cell line , histone h3 , microbiology and biotechnology , chromatin , cell culture , gene expression , promoter , gene , genetics
JMJD3, a Jumonji C family histone demethylase, is induced by transcription factor, nuclear factor‐kappa B (NF‐ κ B), in response to various stimuli. JMJD3 is crucial for erasing histone‐3 lysine‐27 trimethylation (H3K27me3), a modification associated with transcriptional repression and is responsible for the activation of a diverse set of genes. Here, we identify the genes in human leukaemia monocyte (THP‐1) human monocytic cells that are significantly affected by the stable knockdown (kd) of JMJD3. Global gene expression levels were detected in stable JMJD3 knockdown THP‐1 cells and in tumor necrosis factor‐alpha (TNF‐α)‐stimulated JMJD3‐kd THP‐1 cells by using a 12‐plex NimbleGen human whole genome array. In addition, datasets were analysed by using Ingenuity Pathway Analysis. Stable knockdown of JMJD3 in THP‐1 cells affected particularly in expression levels and in downstream effects on inflammatory signalling pathways. JMJD3 attenuation down‐regulates various key genes in NF‐κB, chemokine and CD40 signalling, and mostly affects inflammatory disease response molecules. In addition, chromatin immunoprecipitation revealed that JMJD3‐kd could inhibit several NF‐ κ B‐regulated inflammatory genes by recruiting repressive histone‐3 lysine‐27 trimethylation to their promoters. Moreover, this study significantly highlights the connexion of NF‐ κ B with JMJD3, which suggests an epigenetic regulation in different signalling pathways. Finally, this study establishes novel JMJD3 targets through Ingenuity Pathway Analysis. Copyright © 2012 John Wiley & Sons, Ltd.