Repression of Transcription by HoxC11 upon Phorbol Ester Stimulation

Abstract

Hox genes encode transcription factors with a conserved DNA-binding domain and exhibit similar DNA-binding preferences. The in vivo specificity required for their biological function is brought about by combinatorial interactions with other factors. Such interactions also modulate their activation state. Here we show that HoxC11 can either activate or repress transcription in a signal-specific manner. We report the isolation of HoxC11 in a yeast one-hybrid screen for factors binding to a phorbol-ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) response element (VLTRE), which is also a target for TPA-induced binding of Rel factors in gel-shift experiments. Although we detect no binding of in vitro translated HoxC11 to the TPA response element in EMSA, overexpression of HoxC11 in the HepG2 cell line leads to a complete block of TPA-induced transcription from a VLTRE-luciferase reporter. There is, however, no repression of the basal levels. The repression is furthermore not dependent on homeo-domain DNA binding. Our data suggest an interaction of HoxC11 with the basal-transcription machinery. We propose that HoxC11 is capable of mediating transcriptional activation or repression in a signal-specific manner and that its activation of the DNA target sequence in yeast might reflect in vivo recruitment to the promoter complex.