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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.

SUBMITTER: Benatti P

PROVIDER: S-EPMC4811486 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Benatti Paolo P Chiaramonte Maria Luisa ML Lorenzo Mariangela M Hartley John A JA Hochhauser Daniel D Gnesutta Nerina N Mantovani Roberto R Imbriano Carol C Dolfini Diletta D

Oncotarget 20160101 2

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 S ...[more]

PMID: 26646448

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

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

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