T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro

Rikke H. Lewinsky, Tina G.K. Jensen, Jette Møller, Allan Stensballe, Jørgen Olsen, Jesper T. Troelsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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-13910 variant associated with lactase persistence than the C-13910 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-13910 variant. Supershift analyses show that Oct-1 binds directly to the T-13910 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-13910 variant/LPH promoter constructs only when it is co-expressed with HNF1α. Binding sites for other intestinal transcription factors (GATA-6, HNF4α, 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-13910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.

Original languageEnglish
JournalHuman Molecular Genetics
Volume14
Issue number24
Pages (from-to)3945-3953
Number of pages9
ISSN0964-6906
DOIs
Publication statusPublished - 15 Dec 2005
Externally publishedYes

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