Elf-1 Binds to GGAA Elements on the FcRγ Promoter and Represses Its Expression

Abstract

The Fc receptor (FcR) γ-chain has been shown to be up-regulated in T cells when the TCR ζ-chain is decreased. We demonstrate that Elf-1, but not other Ets family transcription factors, bind to a cluster of GGAA sites located within the 200 bp upstream from the transcription initiation site of the FcRγ promoter. Forced expression of Elf-1 results in the suppression of FcRγ expression, whereas silencing its expression with small interfering RNA Elf-1 results in increased FcRγ expression. Elf-1 represents the first transcription factor identified to be involved in the transcriptional regulation of FcRγ, and cells that fail to express Elf-1, as is the case with human systemic lupus erythematosus T cells, will express FcRγ-chain.

Cooperative Regulation of Fc Receptor γ-Chain Gene Expression by Multiple Transcription Factors, Including Sp1, GABP, and Elf-1

“…Therefore, the ratio of expression levels of GABP and Elf-1, which differs depending on cell types or conditions, might affect the expression level of FcR␥. Consistent with this, Juang et al (34) recently reported that Elf-1 bound to GGAA elements on the FcR␥ promoter and repressed its expression. In their study, Elf-1 bound to multiple elements, including motif A in the region of nt Ϫ141/Ϫ66 (corresponding to nt Ϫ121/Ϫ46 in their study), whereas Sp1 bound to motif A in our study.…”

Decreased NK Cell FcRγ in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study

“…Recently however, Juang and colleagues reported that Elf-1, a member of the Ets family of transcription factors, is a negative transcriptional regulator of FcRγ in human T lymphocytes whereas it is a positive transcriptional regulator for TCRζ in the same cells [27], [28]. Neither the role of Elf-1 in FcRγ expression in NK cells nor the effect of HIV-1 infection on Elf-1 expression is known.…”

How signaling and gene transcription aberrations dictate the systemic lupus erythematosus T cell phenotype

“…Alternatively, TCR engagement causes one abnormality (for example, lipid raft aggregation) that linearly elicits the others. We should note that decreased expression of the DNA-binding form of the transcription factor Elf-1 results both in decreased activity of the TCRz promoter [11] and increased activity of the FcRg promoter [21], explaining, in part, the presence of FcRg and the reciprocal decrease of CD3z in SLE T cells.…”