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Research article2010Peer reviewed

The combination of gene perturbation assay and ChIP-chip reveals functional direct target genes for IRF8 in THP-1 cells

Kubosaki, Atsutaka; Lindgren, Gabriella; Tagami, Michihira; Simon, Christophe; Tomaru, Yasuhiro; Miura, Hisashi; Suzuki, Takahiro; Arner, Erik; Forrest, Alistair R. R.; Irvine, Katharine M.; Schroder, Kate; Hasegawa, Yuki; Kanamori-Katayama, Mutsumi; Rehli, Michael; Hume, David A.; Kawai, Jun; Suzuki, Masanori; Suzuki, Harukazu; Hayashizaki, Yoshihide

Abstract

Gene regulatory networks in living cells are controlled by the interaction of multiple cell type-specific transcription regulators with DNA binding sites in target genes Interferon regulatory factor 8 (IRF8) also known as Interferon consensus sequence binding protein (ICSBP) is a transcription factor expressed predominantly in myeloid and lymphoid cell lineages To find the functional direct target genes of IRF8 the gene expression profiles of siRNA knockdown samples and genome-wide binding locations by ChIP-chip were analyzed in THP-1 myelomonocytic leukemia cells Consequently 84 genes were identified as functional direct targets The ETS family transcription factor PU 1 also known as SPI1 binds to IRF8 and regulates basal transcription in macrophages Using the same approach we identified 53 direct target genes of PU 1 these overlapped with 19 IRF8 targets These 19 genes included key molecules of IFN signaling such as OAS1 and IRF9 but excluded other IFN-related genes amongst the IRF8 functional direct target genes We suggest that IRF8 and PU 1 can have both combined and independent actions on different promoters in myeloid cells (C) 2010 Elsevier Ltd All rights reserved

Keywords

ChIp-chip; IRF8; PU 1; Interferon

Published in

Molecular Immunology
2010, Volume: 47, number: 14, pages: 2295-2302

    UKÄ Subject classification

    Genetics

    Publication identifier

    DOI: https://doi.org/10.1016/j.molimm.2010.05.289

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/32510