14-3-3　proteins　regulate　numerous　cellular　processes　through　interaction　with　a　variety　of　proteins,　and　have　been　identified　as　HNF1　alpha　binding　partner　by　mass　spectrometry　analysis　in　our　previous　study.　In　the　present　study,　the　interaction　between　14-3-3　xi　and　HNF1　alpha　has　been　further　validated　by　in　vivo　and　in　vitro　assays.　Moreover,　we　have　found　that　overexpression　of　14-3-3　xi　potentiated　the　transcriptional　activity　of　HNF1　alpha　in　cultured　cells,　and　silencing　of　14-3-3　xi　by　RNA　interference　in　HepG2　cells　specifically　affected　the　HNF1　alpha-dependent　gene　expression.　Furthermore,　we　have　demonstrated　that　14-3-3　xi　is　recruited　to　endogenous　HNF1　alpha　responsive　promoters　and　enhances　HNF1　alpha　binding　to　its　cognate　DNA　sequences.　In　addition,　we　have　also　provided　evidence　that　the　association　between　HNF1　alpha　and　14-3-3　xi　is　phosphorylation-dependent.　Taken　together,　these　results　suggest　that　14-3-3　xi　may　be　an　endogenous　physiologic　regulator　of　HNF1　alpha.　(c)　2013　Elsevier　B.V.　All　rights　reserved.