The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.

NF-Y activates genes of metabolic pathways altered in cancer cells / P. Benatti, M.L. Chiaramonte, M. Lorenzo, J.A. Hartley, D. Hochhauser, N. Gnesutta, R. Mantovani, C. Imbriano, D. Dolfini. - In: ONCOTARGET. - ISSN 1949-2553. - 7:2(2016 Jan 12), pp. 1633-1650.

NF-Y activates genes of metabolic pathways altered in cancer cells

M.L. Chiaramonte
Secondo
;
M. Lorenzo;N. Gnesutta;R. Mantovani;D. Dolfini
2016-01-12

Abstract

The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.
cancer metabolism; glycolysis; NF-Y; SOCG pathway; transcription; CCAAT-binding factor; cell line, tumor; gene expression profiling; HCT116 cells; HeLa cells; humans; immunoblotting; K562 cells; metabolic networks and pathways; models, genetic; neoplasms; oligonucleotide array sequence analysis; reverse transcriptase polymerase chain reaction; gene expression regulation, neoplastic; RNA interference; oncology
Settore BIO/18 - Genetica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/483192
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