title: Gene networking and inflammatory pathway analysis in a JMJD3 knockdown human monocytic cell line.
abstract: JMJD3, a Jumonji C family histone demethylase, is induced by transcription factor, nuclear factor-kappa B (NF-κB), 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-κB-regulated inflammatory genes by recruiting repressive histone-3 lysine-27 trimethylation to their promoters. Moreover, this study significantly highlights the connexion of NF-κB with JMJD3, which suggests an epigenetic regulation in different signalling pathways. Finally, this study establishes novel JMJD3 targets through Ingenuity Pathway Analysis.
authors.affiliation: Division of Molecular and Life Science, Hanyang University, Ansan, South Korea.
authors.forename: Nando Dulal
authors.initials: ND
authors.lastname: Das
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Choi
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Yoon
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000276:immunology; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human