Ptx1 regulates SF-1 activity by an interaction that mimics the role of the ligand-binding domain

Abstract

Ptx1 (Pitx1) is a bicoid-related homeobox transcription factor expressed from the onset of pituitary development. It was shown to cooperate with cell-restricted factors, such as Pit1, NeuroD1/PanI and steroidogenic factor 1 (SF-1), to establish a combinatorial code conferring lineage- and promoter-specific gene transcription in the pituitary. Transcriptional synergism between Ptx1 and SF-1 on two SF-1 target genes, pituitary luteinizing hormone beta and Müllerian-inhibiting substance (MIS), requires SF-1 binding to DNA and appears to result from direct physical interaction between these two proteins. The interaction between the C-terminus of Ptx1 and the N-terminal half of SF-1 results in transcriptional enhancement that equals the activity of a constitutively active SF-1 mutant and that may mimic the effect of a still unidentified SF-1 ligand. Thus, the unmasking of SF-1 activity by Ptx1 may represent a developmental mechanism to alleviate the need for SF-1 ligand in transcription and, possibly, at critical times during organogenesis.