Editorial Volume 5, Issue 11 pp 789—790

Figure 1. Complex transcriptional repression of BACE1 gene expression by various NR signaling pathways. As shown on left side, calorie restriction leads to activation of AMPK, SIRT1 and PGC-1 and subsequent repression of BACE1 gene expression. At the bottom of the figure, the binding complexes for PPARγ, PGC-1, SIRT1 and NCoR on the PPREs of the BACE1 promoter are shown (Wang, Cell Metab. 2013; 17:685). The binding of other basal transcription factors Sp1, YY1 and HNF-3 are modeled. We speculate that atRA suppresses BACE1 via direct binding of RAR-RXR onto RAR elements that overlap the PPREs. We also predict that estrogen and vitamin D3 mediate their suppressive effects via their respective nuclear receptors ER and VDR through as yet unidentified promoter binding sites. The RAR, ER and VDR may recruit corepressors such as LCoR in a ligand-dependent manner.