Repression of Transcription by HoxC11 upon Phorbol Ester Stimulation

摘要

Hox genes encode transcription factors with a con- served DNA-binding domain and exhibit similar DNA- binding preferences. The in vivo specificity required for their biological function is brought about by com- binatorial interactions with other factors. Such inter- actions also modulate their activation state. Here we show that HoxCll can either activate or repress tran- scription in a signal-specific manner. We report the isolation of HoxCll in a yeast one-hybrid screen for factors binding to a phorbol-ester, 12-0-tetra- decanoylphorbol-13-acetate (TPA) response element (VLTRE), which is also a target for TPA-induced bind- ing of ReI factors in gel-shift experiments. Although we detect no binding of in vitra translated HoxCll to the TPA response element in EM SA, overexpression of HoxCll 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 HoxCll with the basal- transcription machinery. We propose that HoxCll is capable of mediating transcriptional activation or re- pression in a signal-specific manner and that its acti- vation of the DNA target sequence in yeast might re- flect in viva recruitment to the promoter complex.