Background: Control of thioredoxin-interacting protein (TXNIP) expression is critical for pancreatic beta cell survival. Results: FOXO1 binds to the TXNIP promoter; blocks ChREBP occupancy, and inhibits glucose-induced beta cell TXNIP transcription. Conclusion:FOXO1controls glucose-induced gene expression by competing with ChREBP at target promoters, e.g. TXNIP and L-PK. Significance: This represents a novel gene regulatory mechanism and is the first demonstration of FOXO1-ChREBP cross-talk. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.