Defective trophoblast function in mice with a targeted mutation of Ets2

Abstract

Members of the Ets family of transcription factors mediate transcriptional responses of multiple signaling pathways in diverse cell types and organisms. Targeted deletion of the conserved DNA binding domain of the Ets2 transcription factor results in the retardation and death of homozygous mouse embryos before 8.5 days of embryonic development. Defects in extraembryonic tissue gene expression and function include deficient expression of matrix metalloproteinase-9 (MMP-9, gelatinase B), persistent extracellular matrix, and failure of ectoplacental cone proliferation. Mutant embryos were rescued by aggregation with tetraploid mouse embryos, which complement the developmental defects by providing functional extraembryonic tissues. Rescued Ets2-deficient mice are viable and fertile but have wavy hair, curly whiskers, and abnormal hair follicle shape and arrangement, resembling mice with mutations of the EGF receptor or its ligands. However, these mice are not deficient in the production of TGF␣ or the EGF receptor. Homozygous mutant cell lines respond mitogenically to TGF␣, EGF, FGF1, and FGF2. However, FGF fails to induce MMP-13 (collagenase-3) and MMP-3 (stromelysin-1) in the Ets2-deficient fibroblasts. Ectopic expression of Ets2 in the deficient fibroblasts restores expression of both matrix metalloproteinases. Therefore, Ets2 is essential for placental function, mediating growth factor signaling to key target genes including MMP-3, MMP-9, and MMP-13 in different cell types, and for regulating hair development.

IL-2 and long-term T cell activation induce physical and functional interaction between STAT5 and ETS transcription factors in human T cells

“…Ets-1 presence is consistent with its regulatory role in T cell proliferation and apoptosis (Muthusamy et al, 1995), whereas Ets-2 does not appear essential for lymphoid cells (Yamamoto et al, 1998). Ets-1 expression during activation of normal mature T cells is in agreement with the late appearance of the Stat5-Ets complex.…”

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

“…Interestingly, the potential role of Ets-2 in trophectoderm function is not limited to that of the ruminant. Mice deficient in Ets-2 exhibit defective trophectoderm function during the peri-implantation period (24), and this defect can be rescued by ectopic expression of Ets2 through transfection of retroviral vectors at the preimplantation blastocyst stage of development (25). Moreover, Ets-2 regulates a large number of genes whose expression is a typical "signature" of trophoblast (26).…”

Stem cell pluripotency and transcription factor Oct4

“…Silencing of tau interferon genes (IFNτ) appears to be mediated by 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].…”