Diverse genetic regulatory motifs required for murine adenosine deaminase gene expression in the placenta

Daqing Shi, John Winston, Michael R. Blackburn, Surjit K. Datta, Gerri Hanten, Rodney E. Kellems

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Murine adenosine deaminase (ADA) is a ubiquitous purine catabolic enzyme whose expression is subject to developmental and tissue-specific regulation. ADA is enriched in trophoblast cells of the chorioallantoic placenta and is essential for embryonic and fetal development. To begin to understand the genetic pathway controlling Ada gene expression in the placenta, we have identified and characterized a 770-base pair fragment located 5.4 kilobase pairs upstream of the Ada transcription initiation site, which directs reporter gene expression to the placenta of transgenic mice. The expression pattern of the reporter gene reflected that of the endogenous Ada gene in the placenta. Sequence analysis revealed potential binding sites for bHLH and GATA transcription factors. DNase I footprinting defined three protein binding regions, one of which was placenta-specific. Mutations in the potential protein binding sites and footprinting regions resulted in loss of placental expression in transgenic mice. These findings indicate that multiple protein binding motifs are necessary for Ada expression in the placenta.

Original languageEnglish (US)
Pages (from-to)2334-2341
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number4
DOIs
StatePublished - 1997
Externally publishedYes

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Adenosine Deaminase
Gene expression
Placenta
Gene Expression
Genes
Binding Sites
Protein Binding
GATA Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
Transcription Initiation Site
Deoxyribonuclease I
Reporter Genes
Transgenic Mice
Protein Footprinting
Embryonic and Fetal Development
Tissue
Amino Acid Motifs
Trophoblasts
Enzymes
Base Pairing

ASJC Scopus subject areas

  • Biochemistry

Cite this

Diverse genetic regulatory motifs required for murine adenosine deaminase gene expression in the placenta. / Shi, Daqing; Winston, John; Blackburn, Michael R.; Datta, Surjit K.; Hanten, Gerri; Kellems, Rodney E.

In: Journal of Biological Chemistry, Vol. 272, No. 4, 1997, p. 2334-2341.

Research output: Contribution to journalArticle

Shi, Daqing ; Winston, John ; Blackburn, Michael R. ; Datta, Surjit K. ; Hanten, Gerri ; Kellems, Rodney E. / Diverse genetic regulatory motifs required for murine adenosine deaminase gene expression in the placenta. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 4. pp. 2334-2341.
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