title: NF-Y activates genes of metabolic pathways altered in cancer cells.
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.
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Benatti
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Chiaramonte
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Lorenzo
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, Paul O'Gorman Building, University College London, London, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.affiliation: Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, Paul O'Gorman Building, University College London, London, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hochhauser
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.
authors.forename: Nerina
authors.initials: N
authors.lastname: Gnesutta
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mantovani
authors.affiliation: Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Modena, Italy.
authors.forename: Carol
authors.initials: C
authors.lastname: Imbriano
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Dolfini
mesh_terms: D023081:CCAAT-Binding Factor / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D023081:CCAAT-Binding Factor; C492061:NFYA protein, human; C492063:NFYB protein, human
keywords: NF-Y; SOCG pathway; cancer metabolism; glycolysis; transcription