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

Title
Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line
Author
채영규
Keywords
JMJD3; NF-?B; THP-1 cells; IPA; gene networking
Issue Date
2012-04
Publisher
WILEY-BLACKWELL
Citation
CELL BIOCHEMISTRY AND FUNCTION; APR 2012, 30, 3, p224-p232, 9p.
Abstract
JMJD3, a Jumonji C family histone demethylase, is induced by transcription factor, nuclear factor-kappa B (NF-?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-a)-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-?B, chemokine and CD40 signalling, and mostly affects inflammatory disease response molecules. In addition, chromatin immunoprecipitation revealed that JMJD3-kd could inhibit several NF-?B-regulated inflammatory genes by recruiting repressive histone-3 lysine-27 trimethylation to their promoters. Moreover, this study significantly highlights the connexion of NF-?B with JMJD3, which suggests an epigenetic regulation in different signalling pathways. Finally, this study establishes novel JMJD3 targets through Ingenuity Pathway Analysis. Copyright (C) 2012 John Wiley & Sons, Ltd.
URI
http://onlinelibrary.wiley.com/doi/10.1002/cbf.1839/abstracthttp://hdl.handle.net/20.500.11754/43525
ISSN
0263-6484
DOI
0.1002/cbf.1839/abstract
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIONANOTECHNOLOGY(바이오나노학과) > Articles
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