The human zinc finger protein EGR-4 acts as autoregulatory transcriptional repressor

Biochim Biophys Acta. 1997 Nov 1;1354(2):134-44. doi: 10.1016/s0167-4781(97)00084-5.

Abstract

The human EGR-4 (AT133) gene represents one member of a family of four related zinc finger proteins, that are simultaneously and coordinately induced in resting cells upon growth stimulation. In order to characterise the function of the EGR-4 zinc finger protein, we have expressed the protein in the eukaryotic baculovirus system. The recombinant EGR-4 protein has a molecular mass of 78 kDa, as demonstrated by SDS-PAGE and Western blotting. DNA binding studies revealed that the EGR-4 protein binds to the EGR consensus motif GCGTGGGCG, but not to the G-rich regulatory ZIP-element of the human IL-2 gene, that is a binding site for EGR-1. EGR-4 functions as transcriptional repressor. Overexpression of EGR-4 mediates repression of a minimal c-fos promoter through a threefold EGR consensus site. Furthermore the EGR-4 protein displays autoregulatory activities. This protein downregulates expression of its own gene promoter in a dose dependent manner. A G-rich region in the EGR-4 promoter, located at position -106 to -82, could be identified as binding site for the recombinant EGR-4 protein. A comparison of the two related zinc finger proteins EGR-4 and EGR-1 revealed for each protein distinct and specific DNA binding- and transcriptional regulatory activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Cloning, Molecular
  • Consensus Sequence
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Early Growth Response Protein 1
  • Early Growth Response Transcription Factors
  • Gene Expression
  • Gene Expression Regulation*
  • Genes, Reporter
  • Humans
  • Immediate-Early Proteins*
  • Jurkat Cells
  • Promoter Regions, Genetic
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Spodoptera
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Zinc Fingers* / genetics

Substances

  • DNA-Binding Proteins
  • EGR1 protein, human
  • EGR4 protein, human
  • Early Growth Response Protein 1
  • Early Growth Response Transcription Factors
  • Immediate-Early Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Transcription Factors
  • DNA