RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Mol Immunol. 2010 Aug;47(14):2295-302. doi: 10.1016/j.molimm.2010.05.289. Epub 2010 Jun 22.
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.
活细胞中的基因调控网络受多种细胞类型特异性转录调节剂与靶基因 DNA 结合位点相互作用的控制。干扰素调节因子 8（IRF8），也称为干扰素共识序列结合蛋白（ICSBP），是一种主要在髓系和淋巴系细胞谱系中表达的转录因子。为了找到 IRF8 的功能直接靶基因，我们分析了 THP-1 髓样白血病细胞中 siRNA 敲低样品的基因表达谱和 ChIP-chip 的全基因组结合位置。结果，鉴定出 84 个功能性直接靶基因。ETS 家族转录因子 PU.1，也称为 SPI1，与 IRF8 结合并调节巨噬细胞中的基础转录。使用相同的方法，我们鉴定了 53 个 PU.1 的直接靶基因；这些与 19 个 IRF8 靶基因重叠。这 19 个基因包括 IFN 信号的关键分子，如 OAS1 和 IRF9，但在 IRF8 功能直接靶基因中排除了其他 IFN 相关基因。我们认为，IRF8 和 PU.1 可以在髓样细胞中的不同启动子上发挥组合和独立的作用。
