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

Area of Science:

• Molecular Biology
• Cancer Biology
• Metabolic Regulation

Background:

• The transcription factor NF-Y binds to the CCAAT box, a DNA sequence found in promoters of genes overexpressed in tumors.
• Previous studies indicated that NF-Y regulates genes involved in metabolism.

Purpose of the Study:

• To dissect the specific metabolic genes targeted by NF-Y.
• To integrate genomic binding data with gene expression profiles after NF-Y subunit inactivation.

Main Methods:

• Genomic binding analysis of NF-Y.
• Gene expression profiling after inactivation of NF-Y subunits in various cell types.

Main Results:

• NF-Y controls de novo lipid biosynthesis in conjunction with SREBPs.
• NF-Y activates glycolytic genes but represses mitochondrial respiratory genes.
• NF-Y targets key metabolic pathways including SOCG, glutamine, polyamine, and purine biosynthesis.

Conclusions:

• NF-Y orchestrates a metabolic strategy favoring anaerobic energy production and anabolic pathways common in cancer.
• NF-Y directly controls critical cancer-driving metabolic nodes.
• These findings reveal NF-Y's role in reprogramming cellular metabolism for tumor growth.