Figure 3. Menin represses gene expression via multiple mechanisms.

(A) Menin interacts with JunD and recruits the Sin3A/histone deacetylase (HDAC) complex to reduce histone acetylation and suppress the expression of JunD targets such as Gastrin. The endogenous targets of JunD in this setting are unclear. (B) Menin also blocks JNK mediated phosphorylation of JunD, leading to repression of JunD transcriptional targets such as Gastrin. (C) In lung cancer cells, menin recruits EZH2 to the promoter of PTN to increase H3K27 trimethylation, a repressive mark, to downregulate the transcription of PTN. Whether menin directly interacts with EZH2 is yet to be determined (D) Menin can inhibit Hedgehog signaling by interacting with PRMT5 at the Gas1 promoter in pancreatic islets to increase PRMT5-mediated symmetric H4R3 dimethylation, which inhibits the expression of Gas1 and therefore Hedgehog signaling.