Several mechanisms have been proposed for the action of activator proteins. Activator proteins can bind an enhancer and function as nucleation centers for preinitiation transcription complex or they can interact with the general transcriptional factors at the cognate promoter and stabilize the transcription complex. Alternatively, they can recruit chromatin modifying regulators, open chromatin and thus promote transcription. FOXA proteins belong to a unique class of transcription factors that function as pioneer factors, proteins that can bind highly compacted chromatin and alter the chromatin structure and enhance transcription (Zaret et al., 2008). During development FOXA proteins have shown to bind the enhancer of the albumin gene and open the chromatin (Chaya et al., 2001; Cirillo et al., 2002). FOXA1 has also been shown to act as pioneer factor in adult tissues (Carroll et al., 2005; Gao et al., 2003; Zhang et al., 2005). It is possible that FOXA and HNF-1α proteins are acting at the ADH4 enhancer through any one or a combination of these mechanisms.
