Repression of Ets-2-Induced Transactivation of the Tau Interferon Promoter by Oct-4

Abstract

Oct-4 is a POU family transcription factor associated with potentially totipotent cells. Genes expressed in the trophectoderm but not in embryos prior to blastocyst formation may be targets for silencing by Oct-4. Here, we have tested this hypothesis with the tau interferon genes (IFNT genes), which are expressed exclusively in the trophectoderm of bovine embryos. IFNT promoters contain an Ets-2 enhancer, located at ؊79 to ؊70, and are up-regulated about 20-fold by the overexpression of Ets-2 in human JAr choriocarcinoma cells, which are permissive for IFNT expression. This enhancement was reversed in a dose-dependent manner by coexpression of Oct-4 but not either Oct-1 or Oct-2. When cells were transfected with truncated bovine IFNT promoters designed to eliminate potential octamer sites sequentially, luciferase reporter expression from each construct was still silenced by Oct-4. Full repression required both the N-terminal and POU domains of Oct-4, but neither domain used alone was an effective silencer. Oct-4 and Ets-2 formed a complex in vitro in the absence of DNA through binding of the POU domain of Oct-4 to a site located between the "pointed" and DNA binding domains of Ets-2. The two transcription factors were also coimmunoprecipitated after being expressed together in JAr cells. Oct-4, therefore, silences IFNT promoters by quenching Ets-2 transactivation. The POU domain most probably binds to Ets-2 directly, while the N-terminal domain inhibits transcription. These findings provide further evidence that the developmental switch to the trophectoderm is accompanied by the loss of Oct-4 silencing of key genes.

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

“…Ets2-transcriptional regulation of the IFNT promoter is also silenced by Oct4, the hallmark transcription factor of pluripotent cells. We have suggested a model in which the down regulation of Oct4 that accompanies the emergence of trophectoderm releases constraints operating over the expression of IFNT, thereby placing the promoter in a permissive state for subsequent upregulation by lineage-specific factors (27). Observations from this laboratory suggest that the Dlx3/Ets2/AP1 composite element is responsive to both the Ras/MAPK and cAMP/PKA signal transduction pathways and hence to factors that operate through these pathways.…”

Stem cell pluripotency and transcription factor Oct4

“…IFNτ is expressed exclusively in the TE of bovine embryos and activated through the Ets-2 binding enhancer [36]. Ezashi et al reported that Oct4 and Ets-2 could form a complex through interaction between the Oct4 POU domain and the DNA binding domain of Ets-2, and as a result quench the transactivation function of Ets-2 [37]. In trophectodermal cells, Oct4 is downregulated, thus, alleviating the co-repression of Ets-2 to allow the TE specific genes such as IFNτ to be expressed [37].…”

“…Ezashi et al reported that Oct4 and Ets-2 could form a complex through interaction between the Oct4 POU domain and the DNA binding domain of Ets-2, and as a result quench the transactivation function of Ets-2 [37]. In trophectodermal cells, Oct4 is downregulated, thus, alleviating the co-repression of Ets-2 to allow the TE specific genes such as IFNτ to be expressed [37]. These findings provided evidence that the developmental switch could be accomplished by the loss of Oct4 mediated silencing of key genes.…”

Lymphoid Enhancer Factor-1 and ॆ-Catenin Inhibit Runx2-dependent Transcriptional Activation of the Osteocalcin Promoter

“…LEF1 Interacts with the RHD-To determine how LEF1 is suppressing Runx2, we considered five potential mechanisms of transcriptional repression: 1) competition for DNA binding sites, 2) squelching of the basal transcriptional machinery, 3) quenching of the activation properties of DNA-bound Runx2, 4) indirect transcriptional repression by complexing with Runx2 and preventing DNA binding, and 5) co-repressor recruitment (41)(42)(43). Competition is unlikely because a DNA probe containing just the Runx-binding element does not compete with a mOG2 probe for LEF1 (Fig.…”