A Common Set of Gene Regulatory Networks Links Metabolism and Growth Inhibition
| Autor: | Egle Balciunaite, Richard C. Scarpulla, Richard A. Young, Yuval Kluger, Hugh Cam, Brian David Dynlacht, Alexander Spektor, Alexandre Blais |
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| Rok vydání: | 2004 |
| Předmět: |
Amino Acid Motifs
Apoptosis Retinoblastoma-Like Protein p107 E2F4 Transcription Factor Biology Neoplasms Genes Regulator Tumor Cells Cultured Humans NRF1 E2F Molecular Biology Transcription factor E2F4 Oligonucleotide Array Sequence Analysis Genetics Regulation of gene expression Binding Sites Retinoblastoma-Like Protein p130 Nuclear Respiratory Factor 1 Gene Expression Profiling Nuclear Proteins Proteins Promoter Cell Biology Cell biology DNA-Binding Proteins Gene expression profiling Gene Expression Regulation Mitochondrial biogenesis Transcription Factors |
| Zdroj: | Molecular Cell. 16:399-411 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2004.09.037 |
| Popis: | Using genome-wide analysis of transcription factor occupancy, we investigated the mechanisms underlying three mammalian growth arrest pathways that require the pRB tumor suppressor family. We found that p130 and E2F4 cooperatively repress a common set of genes under each growth arrest condition and showed that growth arrest is achieved through repression of a core set of genes involved not only in cell cycle control but also mitochondrial biogenesis and metabolism. Motif-finding algorithms predicted the existence of nuclear respiratory factor-1 (NRF1) binding sites in E2F target promoters, and genome-wide factor binding analysis confirmed our predictions. We showed that NRF1, a factor known to regulate expression of genes involved in mitochondrial function, is a coregulator of a large number of E2F target genes. Our studies provide insights into E2F regulatory circuitry, suggest how factor occupancy can predict the expression signature of a given target gene, and reveal pathways deregulated in human tumors. |
| Databáze: | OpenAIRE |
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