Transcriptional properties of Ptx1 and Ptx2 isoforms

The Ptx (Pitx) family of homeobox transcription factors comprises Ptx1, Ptx2 and Ptx3. Ptx1 and Ptx2 are expressed in the stomodeum and its derivatives including the pituitary, as well as in mesodermal derivatives, whereas Ptx3 is expressed in one neuronol lineage of the brain and in the eyes. A large set of downstream target genes have been identified for Ptx1 in the pituitary gland where it acts as a pan-pituitary regulator of transcription. In particular, Ptx1 contributes to promoter- and lineage-specific transcription by interaction with cell-restricted facto rs such as SF-1, Egr-1, Pit1, and the basic helix-loop-helix heterodimer NeuroD1/Pan1. We describe the cloning from pituitary cells and the characterization of a Ptx1 isoform, named Ptx1b, generated by alternative promoter usage. The two Ptx1 and two Ptx2 isoforms have similar in vitro DNA binding specificities and they all activate transcription driven by a panel of pituitary promoters, including those for proopiomelanocortin, alpha GSU, LH beta, FSH beta, GnRH-R, TSH beta, PRL, and GH. Also like Ptx1, the Ptx1b, Ptx2a, and Ptx2b transcription factors synergize with the structurally unrelated factors SF-1, Egr-1, Pit1, and NeuroD1/Pan1 to activate promoter-specific transcription. In conclusion, the pituitary transcriptional activities of the four Ptx isoforms do not appear to be dependent on the va riant N-termini of these factors. Copyright (C) 2000 S. Karger AG, Basel.