In vivo search for butyrate responsive sequences using transgenic mice carrying (A)γ gene promoter mutants

Betty Sue Pace, Qiliang Li, George Stamatoyannopoulos

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Abstract

We describe an in vivo approach, in transgenic mice, aimed to identify promoter elements responsible for the induction of γ globin expression by butyrate. Transgenic lines carrying human (A)γ gene promoter truncations at position -141, -201, -382, and -730 (A)γ were treated with α amino butyric acid (αABA) and effects on γ globin expression were analyzed at the messenger RNA level. No induction of γ gene expression was observed in animals carrying promoters truncated at positions -141, -201, or -382 (A)γ, suggesting either that butyrate response elements (BRE) are not located in the proximal γ, gene promoter or, if they were, they require the cooperation of upstream sequences for γ gene induction. Two animals from one line carrying the -730 (A)Γ, truncation responded to αABA treatment with significant increases in γ gene expression, indicating that a BRE is located between position -382 and -730 region of the (A)γ gene promoter. Because the maximum induction by αABA is observed in transgenic mice carrying a (A)γ gene promoter extending to nucleotide -1350, it is likely that another butyrate responsive element is located between -730 and -1350 of the (A)γ gene promoter. These results indicate that the transgenic mouse model can be used for identification of DNA regions that contain cis elements involved in γ globin gene inducibility.

Original languageEnglish (US)
Pages (from-to)1079-1083
Number of pages5
JournalBlood
Volume88
Issue number3
Publication statusPublished - Aug 1 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Hematology

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