Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi

نویسندگان

  • Yasuhiro Tomaru
  • Misato Nakanishi
  • Hisashi Miura
  • Yasumasa Kimura
  • Hiroki Ohkawa
  • Yusuke Ohta
  • Yoshihide Hayashizaki
  • Masanori Suzuki
چکیده

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.

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عنوان ژورنال:

دوره 37  شماره 

صفحات  -

تاریخ انتشار 2009