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Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene.

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.

SUBMITTER: Ward RD

PROVIDER: S-EPMC1998882 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene.

Ward Robert D RD Davis Shannon W SW Cho Minchul M Esposito Constance C Lyons Robert H RH Cheng Jan-Fang JF Rubin Edward M EM Rhodes Simon J SJ Raetzman Lori T LT Smith Timothy P L TP Camper Sally A SA

Mammalian genome : official journal of the International Mammalian Genome Society 20070608 6-7

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 fiv ...[more]

PMID: 17557180

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Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene.

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Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene.

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