Transcriptional control of IFNT expression

Abstract

Summary Once interferon-tau (IFNT) had been identified as a Type I IFN in sheep and cattle and its functions characterized, numerous studies were conducted to elucidate transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5/UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT down-regulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.

Heat stress on oocyte or zygote compromises embryo development, impairs interferon tau production and increases reactive oxygen species and oxidative stress in bovine embryos produced in vitro

“…Our results have shown that HS during oocyte maturation, fertilization and/or embryo Trophoblastic cells produce IFNT, which is essential for maternal recognition of pregnancy (Spencer, Johnson, Bazer, & Burghardt, 2004), it is also a good marker for embryonic health (Roberts, Chen, Ezashi, & Walker, 2008). Another approach to investigate embryo/ trophoblast health is to evaluate caudal-type homeobox transcription factor (CDX2), which plays an essential role in trophoblast lineage emergence in ruminants (Ezashi & Imakawa, 2017). Therefore, the CDX2 antibody was used to assess trophoblastic cells on Day 7 embryos.…”

Desenvolvimento embrionário em búfalos (Bubalus bubalis Linnaeus, 1758)

“…EZASHI;GHOSH;ROBERTS, 2001). A proteína Oct-4 mantida no TE pode suprimir a expressão de genes linhagem-específicos extra-embrionárias durante o desenvolvimento da pré-implantação e permitir a ploriferação extensiva do…”

30 years on from the molecular cloning of interferon-tau

“…Instead, I came to the conclusion that the uniqueness of the IFNT system is in the highly conserved transcriptional control regions of its genes, which lack the virally inducible features of other type I IFN. Accordingly, I asked two pioneers in the IFNT field, Toshihiko Ezashi and Kazuhiko Imakawa to review what is currently known about the controls operating over transcription of IFNT in trophoblast (Ezashi & Imakawa 2017). Dr Imakawa was, of course, the first author on the 1987 Nature paper, while Dr Ezashi had described the ETS2/AP1/DLX3 enhancer element crucial in regulating IFNT gene expression (Roberts et al 2003).…”