Abstract
The pituitary gland has provided unique insight into molecular mechanisms and regulatory factors controlling 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenocorticotropic Hormone / deficiency
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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Cell Differentiation
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Cell Line
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Child
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Chlorocebus aethiops
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Conserved Sequence
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism*
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Humans
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mutation
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Paired Box Transcription Factors
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Pituitary Gland / cytology
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Pituitary Gland / metabolism*
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Pituitary Neoplasms
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Polymerase Chain Reaction
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Pro-Opiomelanocortin / genetics*
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Sequence Alignment
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Sequence Homology, Amino Acid
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T-Box Domain Proteins
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Transcription Factors / chemistry
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Transcription Factors / genetics*
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Transcription Factors / metabolism*
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Transcription, Genetic*
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Transfection
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Tumor Cells, Cultured
Substances
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Homeodomain Proteins
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Paired Box Transcription Factors
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T-Box Domain Proteins
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TBX19 protein, human
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Tbx19 protein, mouse
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Transcription Factors
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homeobox protein PITX1
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Pro-Opiomelanocortin
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Adrenocorticotropic Hormone