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

Aaron D. Showalter, Timothy P L Smith, Gary L. Bennett, Kyle W. Sloop, Julie A. Whitsett, Simon Rhodes

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalGene
Volume291
Issue number1-2
DOIs
StatePublished - May 29 2002

Fingerprint

Genes
Proteins
Transcription Factors
Organogenesis
Quantitative Trait Loci
Pituitary Gland
Ovulation
Introns
Transcriptional Activation
Organism Cloning
Exons
Chromosomes
Alleles
Prophet of Pit-1 protein
Mutation
DNA
Combined Pituitary Hormone Deficiency

Keywords

  • Alleles
  • Homeodomain
  • Human
  • Ovulation
  • Pituitary

ASJC Scopus subject areas

  • Genetics

Cite this

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. / Showalter, Aaron D.; Smith, Timothy P L; Bennett, Gary L.; Sloop, Kyle W.; Whitsett, Julie A.; Rhodes, Simon.

In: Gene, Vol. 291, No. 1-2, 29.05.2002, p. 211-221.

Research output: Contribution to journalArticle

Showalter, Aaron D. ; Smith, Timothy P L ; Bennett, Gary L. ; Sloop, Kyle W. ; Whitsett, Julie A. ; Rhodes, Simon. / 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. In: Gene. 2002 ; Vol. 291, No. 1-2. pp. 211-221.
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