TXNIP was previously identified as a transcriptional target of the ChREBP transcription factor in response to elevated carbohydrate and adenosine nucleotides (Minn et al., 2005; Yu and Luo, 2009). While significant, ChREBP has a modest effect on TXNIP transcription under ER stress: ChREBP undergoes nuclear translocation and ChREBP mRNA increases slightly (Figure S5). ER stress may overlap with hyperglycemic signals that activate ChREBP; intriguingly, IRE1α is also partially activated by adenosine nucleotides or hyperglycemia (Lipson et al., 2006). An accompanying manuscript from Fumihiko Urano’s lab also explores PERK and ChREBP transcriptional control of TXNIP, which may be complementary to IRE1α’s post-transcriptional control. Combining post-transcriptional mRNA stabilization with transcriptional synthesis may allow cells to robustly and rapidly commit to self-destruction under high ER stress. Control of gene expression under ER stress through micro RNAs may be widespread, as in other biological processes.
