A ternary complex factor-dependent mechanism mediates induction of egr-1 through selective serum response elements following antigen receptor cross-linking in B lymphocytes.
Induction of the primary response gene egr-1 occurs rapidly following antigen receptor cross-linking in B lymphocytes. Antisense studies have demonstrated that this induction is necessary for their subsequent activation to this signal. The present study examines the molecular mechanism whereby the receptor-generated signals interact with the egr-1 promoter to elicit transcription. Deletion mapping and point mutations have indicated that two of the five serum response elements (SREs) in the egr-1 promoter can mediate induction. Of the two critical SREs, both are capable of mediating maximal induction even in the absence of the other SRE. Our results also indicate that adjacent Ets motifs are necessary for induction. Like the c-fos SRE, the egr-1 SRE/Ets sites are occupied by a multiprotein (ternary) complex containing a homodimer of serum response factor and an unidentified member of the Ets family of transcription factors. The identification of a ternary complex-dependent mechanism of egr-1 induction, along with selective utilization of SREs in B lymphocytes, suggests that a complicated array of signaling cascades interacts with unique combinations of regulatory elements in the egr-1 promoter in different cell types.
McMahon
S B
SB
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Monroe
J G
JG
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D026362:Serum Response Factor; D013154:Spleen; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D026362:Serum Response Factor; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase