Transcriptional properties of Ptx1 and Ptx2 isoforms

The Ptx (Pitx) family of homeobox transcription factors comprises Ptx1, Ptx 2 and Ptx3. Ptx1 and Ptx2 are expressed in the stomodeum and its derivative s including the pituitary, as well as in mesodermal derivatives, whereas Pt x3 is expressed in one neuronol lineage of the brain and in the eyes. A lar ge set of downstream target genes have been identified for Ptx1 in the pitu itary gland where it acts as a pan-pituitary regulator of transcription. In particular, Ptx1 contributes to promoter- and lineage-specific transcripti on 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 cl oning from pituitary cells and the characterization of a Ptx1 isoform, name d Ptx1b, generated by alternative promoter usage. The two Ptx1 and two Ptx2 isoforms have similar in vitro DNA binding specificities and they all acti vate transcription driven by a panel of pituitary promoters, including thos e for proopiomelanocortin, alpha GSU, LH beta, FSH beta, GnRH-R, TSH beta, PRL, and GH. Also like Ptx1, the Ptx1b, Ptx2a, and Ptx2b transcription fact ors synergize with the structurally unrelated factors SF-1, Egr-1, Pit1, an d NeuroD1/Pan1 to activate promoter-specific transcription. In conclusion, the pituitary transcriptional activities of the four Ptx isoforms do not ap pear to be dependent on the va riant N-termini of these factors. Copyright (C) 2000 S. Karger AG, Basel.