Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tomaru, Yasuhiro, Nakanishi, Misato, Miura, Hisashi, Kimura, Yasumasa, Ohkawa, Hiroki, Ohta, Yusuke, Hayashizaki, Yoshihide, Suzuki, Masanori
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651797/
https://www.ncbi.nlm.nih.gov/pubmed/19129217
http://dx.doi.org/10.1093/nar/gkn1028
_version_ 1782165190454804480
author Tomaru, Yasuhiro
Nakanishi, Misato
Miura, Hisashi
Kimura, Yasumasa
Ohkawa, Hiroki
Ohta, Yusuke
Hayashizaki, Yoshihide
Suzuki, Masanori
author_facet Tomaru, Yasuhiro
Nakanishi, Misato
Miura, Hisashi
Kimura, Yasumasa
Ohkawa, Hiroki
Ohta, Yusuke
Hayashizaki, Yoshihide
Suzuki, Masanori
author_sort Tomaru, Yasuhiro
collection PubMed
description 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.
format Text
id pubmed-2651797
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-26517972009-03-13 Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi Tomaru, Yasuhiro Nakanishi, Misato Miura, Hisashi Kimura, Yasumasa Ohkawa, Hiroki Ohta, Yusuke Hayashizaki, Yoshihide Suzuki, Masanori Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2009-03 2009-01-07 /pmc/articles/PMC2651797/ /pubmed/19129217 http://dx.doi.org/10.1093/nar/gkn1028 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Tomaru, Yasuhiro
Nakanishi, Misato
Miura, Hisashi
Kimura, Yasumasa
Ohkawa, Hiroki
Ohta, Yusuke
Hayashizaki, Yoshihide
Suzuki, Masanori
Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title_full Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title_fullStr Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title_full_unstemmed Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title_short Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi
title_sort identification of an inter-transcription factor regulatory network in human hepatoma cells by matrix rnai
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651797/
https://www.ncbi.nlm.nih.gov/pubmed/19129217
http://dx.doi.org/10.1093/nar/gkn1028
work_keys_str_mv AT tomaruyasuhiro identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT nakanishimisato identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT miurahisashi identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT kimurayasumasa identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT ohkawahiroki identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT ohtayusuke identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT hayashizakiyoshihide identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai
AT suzukimasanori identificationofanintertranscriptionfactorregulatorynetworkinhumanhepatomacellsbymatrixrnai