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A Pituitary Cell-Restricted T Box Factor, Tpit, Activates POMC Transcription in Cooperation with Pitx Homeoproteins

2001; Cell Press; Volume: 104; Issue: 6 Linguagem: Inglês

10.1016/s0092-8674(01)00282-3

1097-4172

Bruno Lamolet, Anne-Marie Pulichino, Thomas Lamonerie, Yves Gauthier, Thierry Brue, A Enjalbert, Jacques Drouin,

Growth Hormone and Insulin-like Growth Factors

Abstract The pituitary gland has provided unique insight into molecular mechanisms and regulatory factors controling both differentiation and gene transcription. We identified Tpit, a novel T box factor only present in the two pituitary POMC-expressing lineages, the corticotrophs and melanotrophs, and apparently in no other tissue, including hypothalamic POMC neurons. In pituitary cells, Tpit activation of POMC gene transcription requires cooperation with Pitx1, the two factors binding to contiguous sites within the same regulatory element. In gain-of-function experiments, Tpit induces POMC expression in undifferentiated pituitary cells, indicating that it can initiate differentiation into POMC-expressing lineages. TPIT gene mutations were found in patients with isolated deficiency of pituitary POMC-derived ACTH, in support of an essential role of Tpit for differentiation of the pituitary POMC lineage.