Control of interferon-τ gene expression by Ets-2

Abstract

Expression of the multiple interferon-(IFN-) genes is restricted to embryonic trophectoderm of ruminant ungulate species for a few days in early pregnancy. The promoter regions of these genes are highly conserved. A proximal (bp ؊91 to ؊69) sequence has been implicated in controlling trophoblast-specific expression. Here it was used as a target for yeast one-hybrid screening of a day 13 conceptus cDNA library. Two transcription factors of the Ets family, Ets-2 and GABP␣, were identified, consistent with the observation that active ovine IFN-genes contain a single 10-bp Ets motif (core: GGAA) in the proximal segment, whereas three known inactive ovine genes contain a mutated core motif (TGAA). Cotransfection of a promoter-(؊126 to ؉50) luciferase reporter construct from an active gene (bovineIFN-1; boIFNT1) and an Ets-2 expression plasmid in human JAr cells provided up to a 30-fold increase in reporter expression, whereas promoters from inactive genes were not transactivated. GABP␣ alone was ineffective and had only a Ϸ2-fold positive effect when coexpressed with its partner GABP␤. Other Ets-related transcription factors, which were not detected in the genetic screen, also provided a range of lesser transactivation effects. Coexpression of Ets-2 and activated Ras failed to transactivate the IFNT promoter greater than Ets-2 alone in JAr cells. The presence of Ets-2 in nuclei of embryonic trophectoderm was confirmed immunocytochemically. Together, these data suggest that Ets-2 plays a role in the transient expression of the nonvirally inducible IFNT genes.

Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy

“…Transfection experiments confirmed that the proximal-most site, is essential for gene expression. When part of this region was used as a target for yeast one-hybrid screening of a Day 13 conceptus library, the nuclear protein, Ets-2, was identified as binding to this site and to activate transcription (22). This element is adjacent to a putative AP1 site and two helical turns upstream of a binding site for the homeobox protein Dlx3.…”

Role for Ets-2Thr-72 Transcription Factor in Stage-specific Thymocyte Development and Survival

“…Threonine 72-In a variety of cell types Ets-2 is regulated by the Ras-dependent MAPK ERK (10,11). Activated ERK phosphorylates Ets-2 at threonine 72, which results in transcriptional transactivation.…”

“…Oncogenic (constitutively active) Ras in conjunction with Ets-2 super-activates promoters containing Ets-binding sites (10,11). Ras pathwaymediated activation of Ets-2 occurs through a conserved MAPK-docking motif, PLLTP, contained within amino acids 69 -73 of the Ets-2 protein.…”

Biodiversity of multiple Pregnancy-Associated Glycoprotein (PAG) family: gene cloning and chorionic protein purification in domestic and wild eutherians (Placentalia) – a review

“…Presumably, Ets factors can play an important role in the activation of the PAG genes. The involvement of Ets factors in the control of IFN-τ has been shown in ruminants [30,31] or in specific control of human gene expression [32]. The activation of the PAG genes may also be controlled by other mechanisms or transcription factors that are indicated for cathepsin D promoter [33] or other placental promoters of hCG [34], Prl [35], Prl-like placental proteins [36,37] and lactogens [38].…”