Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.1.1.1 (
alcohol dehydrogenase
)
9,284
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Comparative genomics reveals functional transcriptional control sequences in the Prop1 gene. 1755 80
