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Title: DIFFERENTIAL CONSERVATION OF TRANSCRIPTIONAL DOMAINS OF MAMMALIAN PROPHET OF PIT-1 PROTEINS REVEALED BY STRUCTURAL STUDIES OF THE BOVINE GENE AND COMPARATIVE FUNCTIONAL ANALYSIS OF THE PROTEIN

Author
item SHOWALTER, AARON - INDIANA UNIV-PURDUE
item Smith, Timothy - Tim
item Bennett, Gary
item SLOOP, KYLE - INDIANA UNIV-PURDUE
item WHITSETT, JULIE - INDIANA UNIV-PURDUE
item RHODES, SIMON - INDIANA UNIV-PURDUE

Submitted to: Gene
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/5/2002
Publication Date: 7/10/2002
Citation: Showalter, A.D., Smith, T.P., Bennett, G.L., Sloop, K.W., Whitsett, J.A., Rhodes, S.J. 2002. Differential conservation of transcriptional domains of mammalian prophet of pit-1 proteins revealed by structural studies of the bovine gene and comparative functional analysis of the protein. Gene. 291:211-221.

Interpretive Summary: The research examined the bovine version of a gene, called PROP1, that is critical to development and function of the pituitary gland. This gland is the source of a number of important hormones that regulate bodily functions such as ovulation and puberty. Two distinct but very similar versions of the PROP1 protein were discovered to exist in cattle. One form closely resembles PROP1 protein from other species, while the other has a particular change in the sequence of amino acids not yet observed in other species. The ability of this form to direct expression of other genes was found to be defective in this bovine-specific form, suggesting that the amino acid sequence change has potential impact on function of the pituitary gland. The gene was mapped to a part of bovine chromosome 7 that we previously showed carries a locus affecting ovulation rate in high twinning rate cattle, suggesting the possibility that this amino acid sequence change may represent a mutation causing a difference in ovulation rate.

Technical Abstract: The Prophet of Pit-1 (PROP1) gene encodes a paired class homeodomain transcription factor that is exclusively expressed in the developing mammalian pituitary gland. PROP1 function is essential for anterior pituitary organogenesis, and heritable mutations in the gene are associated with combined pituitary hormone deficiency in human patients and animals. By cloning the bovine PROP1 gene and by comparative analysis, we demonstrate that the homeodomains and carboxyl termini of mammalian PROP1 proteins are highly conserved while the amino termini are diverged. Whereas the carboxyl termini of the human and bovine PROP1 proteins contain potent transcriptional activation domains, the amino termini and homeodomains have repressive activities. The bovine PROP1 gene has four exons and three introns and maps to a region of chromosome seven carrying a quantitative trait locus affecting ovulation rate. Two alleles of the bovine gene were found that encode distinct protein products with different DNA binding and transcriptional activities. These experiments demonstrate that mammalian PROP1 genes encode proteins with complex regulatory capacities and that modest changes in protein sequence can significantly alter the activity of this pituitary developmental transcription factor.