The human zinc finger protein EGR-4 acts as autoregulatory transcriptional repressor.
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.
Zipfel
P F
PF
Bernhard Nocht Institute for Tropical Medicine, Department for Molecular Biology, Hamburg, Germany.
Decker
E L
EL
Holst
C
C
Skerka
C
C
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D051765:Early Growth Response Transcription Factors; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D017874:Immediate-Early Proteins; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; C111028:EGR4 protein, human; D051766:Early Growth Response Protein 1; D051765:Early Growth Response Transcription Factors; D017874:Immediate-Early Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA