Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene

Robert D. Ward, Shannon W. Davis, MinChul Cho, Constance Esposito, Robert H. Lyons, Jan Fang Cheng, Edward M. Rubin, Simon Rhodes, Lori T. Raetzman, Timothy P L Smith, Sally A. Camper

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Mutations in PROP1 are a common genetic cause of multiple pituitary hormone deficiency (MPHD). We used a comparative genomics approach to predict the transcriptional regulatory domains of Prop1 and tested them in cell culture and mice. A BAC transgene containing Prop1 completely rescues the Prop1 mutant phenotype, demonstrating that the regulatory elements necessary for proper PROP1 transcription are contained within the BAC. We generated DNA sequences from the PROP1 genes in lemur, pig, and five different primate species. Comparison of these with available human and mouse PROP1 sequences identified three putative regulatory sequences that are highly conserved. These are located in the PROP1 promoter proximal region, within the first intron of PROP1, and downstream of PROP1. Each of the conserved elements elicited orientation-specific enhancer activity in the context of the Drosophila alcohol dehydrogenase minimal promoter in both heterologous and pituitary-derived cells lines. The intronic element is sufficient to confer dorsal expansion of the pituitary expression domain of a transgene, suggesting that this element is important for the normal spatial expression of endogenous Prop1 during pituitary development. This study illustrates the usefulness of a comparative genomics approach in the identification of regulatory elements that may be the site of mutations responsible for some cases of MPHD.

Original languageEnglish
Pages (from-to)521-537
Number of pages17
JournalMammalian Genome
Volume18
Issue number6-7
DOIs
StatePublished - Jul 2007

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Pituitary Hormones
Genomics
Transgenes
Lemur
Mutation
Conserved Sequence
Genetic Promoter Regions
Introns
Primates
Genes
Swine
Cell Culture Techniques
Phenotype
Cell Line
Drosophila ADH protein

ASJC Scopus subject areas

  • Genetics

Cite this

Ward, R. D., Davis, S. W., Cho, M., Esposito, C., Lyons, R. H., Cheng, J. F., ... Camper, S. A. (2007). Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. Mammalian Genome, 18(6-7), 521-537. https://doi.org/10.1007/s00335-007-9008-6

Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. / Ward, Robert D.; Davis, Shannon W.; Cho, MinChul; Esposito, Constance; Lyons, Robert H.; Cheng, Jan Fang; Rubin, Edward M.; Rhodes, Simon; Raetzman, Lori T.; Smith, Timothy P L; Camper, Sally A.

In: Mammalian Genome, Vol. 18, No. 6-7, 07.2007, p. 521-537.

Research output: Contribution to journalArticle

Ward, RD, Davis, SW, Cho, M, Esposito, C, Lyons, RH, Cheng, JF, Rubin, EM, Rhodes, S, Raetzman, LT, Smith, TPL & Camper, SA 2007, 'Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene', Mammalian Genome, vol. 18, no. 6-7, pp. 521-537. https://doi.org/10.1007/s00335-007-9008-6
Ward, Robert D. ; Davis, Shannon W. ; Cho, MinChul ; Esposito, Constance ; Lyons, Robert H. ; Cheng, Jan Fang ; Rubin, Edward M. ; Rhodes, Simon ; Raetzman, Lori T. ; Smith, Timothy P L ; Camper, Sally A. / Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. In: Mammalian Genome. 2007 ; Vol. 18, No. 6-7. pp. 521-537.
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