Research Papers:
NFY activates genes of metabolic pathways altered in cancer cells
PDF | Full Text | Supplementary Files | How to cite
Metrics: PDF 4014 views | Full Text 5626 views
Paolo Benatti1, Maria Luisa Chiaramonte2, Mariangela Lorenzo2, John A. Hartley3, Daniel Hochhauser3, Nerina Gnesutta2, Roberto Mantovani2, Carol Imbriano1 and Diletta Dolfini2
1 Dipartimento di Scienze della Vita, Università di Modena e Reggio Emilia, Modena, Italy
2 Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy
3 Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, Paul O’Gorman Building, University College London, London, UK
Correspondence to:
Diletta Dolfini, email:
Keywords: transcription, cancer metabolism, NF-Y, glycolysis, SOCG pathway
Received: July 14, 2015 Accepted: November 15, 2015 Published: December 03, 2015
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.