Effects of interactions of hepatocyte nuclear factor 4alpha isoforms with coactivators and corepressors are promoter-specific.

The gene encoding hepatocyte nuclear factor 4alpha (HNF4alpha) possesses two alternative promoters responsible for developmental and tissue-specific expression of HNF4alpha1 and HNF4alpha7. The two isoforms possess different N-termini and exhibit distinct transactivation properties. We show here for the first time that the effects mediated by HNF4alpha isoforms in concert with three different coregulators result in promoter-specific responses. Transcript levels of silencing mediator for retinoid and thyroid receptors and glucocorticoid receptor interacting protein-1 in the liver are reduced at birth, a time point when many genes are strongly activated, suggesting that the effects of coregulators on HNF4alpha activity in vivo could be determined by the levels of their expression as well as by the target promoter.