Functional significance of an overlapping consensus binding motif for Sp1 and Zif268 in the murine adenosine deaminase gene promoter

Susan L. Ackerman, Audrey G. Minden, Gregg T. Williams, Chefin Bobonis, Cho Yau Yeung

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

The murine adenosine deaminase (ADA) gene has a (G+C)-rich promoter that can support diverse tissue-specific gene expression. By using deletion and mutation analyses, we have identified a cis-acting "represser" element located immediately upstream of the proximal Sp1 binding site in the ADA gene promoter. This repressor element was localized to a binding site for the immediate-early, serumresponsive, DNA binding factor Zif268. This Zif268 binding site partially overlaps a binding site for the general transcription activator Spl. Disruption of the Zif268 binding site without disturbing the Sp1 binding motif abolished Zif268 binding and resulted in significantly elevated promoter function. Conversely, disruption of the proximal consensus Sp1 binding motif without disturbing the Zif268 binding site resulted in a loss of Sp1 binding at that region and greatly reduced promoter activity. Our results suggest that one function of Zif268 may be to down-regulate this type of mammalian gene promoter by competing with Sp1 for binding to the overlapping binding motif.

Original languageEnglish (US)
Pages (from-to)7523-7527
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number17
DOIs
StatePublished - 1991

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • (G+C)-rich promoter
  • Negative regulation
  • Transcription factors

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