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T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro.
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- Additional Information
- Source:
Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0964-6906 (Print) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE
- Publication Information:
Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992-
- Subject Terms:
- Abstract:
Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13,910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13,910 variant associated with lactase persistence than the C-13,910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13,910 variant. Supershift analyses show that Oct-1 binds directly to the T-13,910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13,910 variant/LPH promoter constructs only when it is co-expressed with HNF1alpha. Binding sites for other intestinal transcription factors (GATA-6, HNF4alpha, Fox and Cdx-2) were identified in the region of the -13,910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13,910 region. The data suggest that the binding of Oct-1 to the T-13,910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.
- Accession Number:
0 (Hepatocyte Nuclear Factor 1-alpha)
0 (Octamer Transcription Factor-1)
0 (Transcription Factors)
EC 1.2.1.9 (Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+))
EC 3.2.1.108 (Lactase)
EC 3.2.1.62 (Lactase-Phlorizin Hydrolase)
- Publication Date:
Date Created: 20051123 Date Completed: 20060310 Latest Revision: 20220310
- Publication Date:
20240829
- Accession Number:
10.1093/hmg/ddi418
- Accession Number:
16301215
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