FIGURE 8.

Diagram depicting the mode of action by which energy restriction activates KLF6 tumor suppressor gene expression. Previously, we reported the mechanistic link between energy restriction and β-TrCP-mediated proteasomal degradation of Sp1 (8, 20). Here, we extend our understanding that ERMA-mediated Sp1 down-regulation facilitates the transcriptional repression of HDAC1–4 and H3K4DMs (RBP2, PLU-1, and LSD1), resulting in increased histone H3 acetylation and H3K4 methylation. Evidence suggests that enhanced occupancy of the active histone marks Ac-H3 and H3K4Me3 in the promoter region of the KLF6 gene gives rise to KLF6 transcriptional activation. As KLF6 regulates the expression of many proapoptotic genes, this epigenetic activation plays a role in ERMA-induced apoptosis.