Elf-1 regulates basal expression from the T cell antigen receptor zeta-chain gene promoter.
In mature T cells, limited synthesis of the TCR-zeta subunit is primarily responsible for regulating surface expression of TCRs. Transcription of zeta is directed by a complex promoter that includes two potential binding sites for the Ets family of transcription factors at -52 (zEBS1) and -135 (zEBS2). Mutation of these two sites results in a marked reduction of transcription from this promoter. Using electrophoretic mobility shift analysis, Elf-1 was demonstrated to be the Ets family member that binds to these sites. One site, zEBS1, matches the optimal Elf-1 consensus sequence in eight of nine bases, making it the best match of any known mammalian Elf-1 binding site. A role for Elf-1 in TCR-zeta trans-activation was confirmed by ectopic expression of Elf-1 in COS-7 cells. This resulted in an increase in TCR-zeta promoter activity that mapped to zEBS1 and zEBS2. Additional support for the involvement of Elf-1 in TCR-zeta trans-activation derives from the finding that a GAL4-Elf-1 fusion protein trans-activated TCR-zeta promoter constructs that had been modified to contain GAL4 DNA binding sites. These results demonstrate that Elf-1 plays an essential role in the trans-activation of a constitutively expressed T cell-specific gene, and that trans-activation occurs in the context of the native promoter in both lymphoid and nonlymphoid cells. Taken together with the existing literature, these data also suggest that the requirement for inducible factors in Elf-1-mediated trans-activation may decrease as the affinity and number of Elf-1 sites increase.
Rellahan
B L
BL
Laboratory of Immunobiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. rellahan@a1.cber.fda.gov
Jensen
J P
JP
Howcroft
T K
TK
Singer
D S
DS
Bonvini
E
E
Weissman
A M
AM
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; C054979:antigen T cell receptor, zeta chain