Advertisement

Rheumatology International

, Volume 18, Issue 5–6, pp 207–214 | Cite as

Analysis of functional elements in the human Egr-1 gene promoter

  • W. K. Aicher
  • K. M. Sakamoto
  • A. Hack
  • H. Eibel
ORIGINAL ARTICLE

Abstract

The early growth response (Egr)-1 gene encoding a zinc-finger transcription factor is transiently induced in many different cell types upon various differentiation signals. However, in synovial fibroblasts of rheumatoid arthritis patients, Egr-1 is constitutively expressed at high levels, and several genes with Egr-1 binding sites in their promoter regions have been associated with disease progression of RA. We analyzed the control of Egr-1 transcription by characterizing those regulatory elements in the Egr-1 promoter that induce Egr-1 expression in fibroblasts. Using reporter gene assays and deletion mutants of the Egr-1 promoter we could demonstrate that Egr-1 transcription is mainly activated by a single serum response element, whereas other transcription factor binding sites, including binding sites for AP-1 or Egr-1, were found to play a minor role. Furthermore, we identified a novel regulatory element in the human Egr-1 promoter similar to a NFκ-B binding site. Deletion of this element enhanced Egr-1 promoter activity in 3T3 but not in L929 fibroblasts. Stimulation by phorbolester induced only transient Egr-1 expression in 3T3 fibroblasts but a extended expression of Egr-1 in L929 cells. These data suggest that in fibroblasts the most proximal serum response element in the Egr-1 promoter represents the major activation site, whereas binding of the NFkB-like factor may serve as negative regulatory signal for Egr-1 transcription in fibroblasts.

Key words Egr-1 Promoter SRE Regulation Fibroblasts 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • W. K. Aicher
    • 1
  • K. M. Sakamoto
    • 2
  • A. Hack
    • 1
  • H. Eibel
    • 3
  1. 1.Department of Orthopedic Surgery, Research Laboratory University of Tübingen Medical Center, D-72070 Tübingen, GermanyDE
  2. 2.Department of Pediatrics, Division of Hematology-Oncology, and Department of Pathology, Mattel's Childrens Hospital at UCLA and UCLA School of Medicine, Los Angeles, CA 90095-1752, USAUS
  3. 3.Clinical Research Unit for Rheumatology, University Hospital Freiburg, Breisacher Strasse 64, D-79106 Freiburg, Germany e-mail: eibel@nz11.ukl.uni-freiburg.de, Tel.: +49-751-270-5294, Fax: +49-761-270-5298DE

Personalised recommendations