The regulatory hotspot underlying the Chr 15 trans-band has previously been implicated as a regulator of two ethanol behavioral phenotypes, including an ethanol preference QTL mapped using congenic lines derived from B6 and BALB/cJ mice [56]; as well as a QTL underlying loss of righting due to ethanol [57], [58]. The primary candidate regulator of this trans-band was Nell2 (Protein kinase C binding protein), which showed the highest regional response to ethanol. Nell2 was an important hub of ErGeN1, as the network's fifth most central gene. While Nell2's baseline transcription was strongly regulated by a cis eQTL, its ethanol response was modulated by the Chr 13 regulatory hotspot.
