Published online Jul 6, 2015. doi: 10.5527/wjn.v4.i3.363
Peer-review started: November 9, 2014
First decision: November 27, 2014
Revised: May 6, 2015
Accepted: May 16, 2015
Article in press: May 18, 2015
Published online: July 6, 2015
Core tip: The epithelial Na+ channel (ENaC) is a key player in sodium transport and blood pressure control. This minireview summarizes the epigenetic mechanisms governing the transcription of αENaC. The epigenetic control involves Dot1a-Af9-mediated repression through targeted hypermethylation of histone H3 K79. Aldosterone relieves the repression by decreasing Dot1a and Af9 mRNA levels and by weakening the protein-protein interaction between Dot1a and Af9 interaction via Sgk1-catalyzed Af9 phosphorylation. Aldosterone-independent mechanism involves Af17 as a competitor of Af9 for binding Dot1a and stimulator of Dot1a nuclear export. Af17-/- mice exhibit decreased Na+ reabsorption and lowered blood pressure, indicating the significance of this epigenetic control.