title: Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi.
abstract: Transcriptional regulation by transcriptional regulatory factors (TRFs) of their target TRF genes is central to the control of gene expression. To study a static multi-tiered inter-TRF regulatory network in the human hepatoma cells, we have applied a Matrix RNAi approach in which siRNA knockdown and quantitative RT-PCR are used in combination on the same set of TRFs to determine their interdependencies. This approach focusing on several liver-enriched TRF families, each of which consists of structurally homologous members, revealed many significant regulatory relationships. These include the cross-talks between hepatocyte nuclear factors (HNFs) and the other TRF groups such as CCAAT/enhancer-binding proteins (CEBPs), retinoic acid receptors (RARs), retinoid receptors (RXRs) and RAR-related orphan receptors (RORs), which play key regulatory functions in human hepatocytes and liver. In addition, various multi-component regulatory motifs, which make up the complex inter-TRF regulatory network, were identified. A large part of the regulatory edges identified by the Matrix RNAi approach could be confirmed by chromatin immunoprecipitation. The resultant significant edges enabled us to depict the inter-TRF TRN forming an apparent regulatory hierarchy of (FOXA1, RXRA) --> TCF1 --> (HNF4A, ONECUT1) --> (RORC, CEBPA) as the main streamline.
authors.affiliation: OMICS Sciences Center (OSC), RIKEN Yokohama Institute 1-7-22 Suehiro-Cho, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tomaru
authors.forename: Misato
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Miura
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohkawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohta
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D053263:Gene Regulatory Networks; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors