Evolution and functions of Oct4 homologs in non-mammalian vertebrates.

PouV class transcription factor Oct4/Pou5f1 is a central regulator of indefinite pluripotency in mammalian embryonic stem cells (ESCs) but also participates in cell lineage specification in mouse embryos and in differentiating cell cultures. The molecular basis for this versatility, which is shared between Oct4 and its non-mammalian homologs Pou5f1 and Pou5f3, is not yet completely understood. Here, I review the current understanding of the evolution of PouV class transcription factors and discuss equivalent and diverse roles of Oct4 homologs in pluripotency, differentiation, and cell behavior in different vertebrate embryos. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin.

Onichtchouk D 《-》

Zygotic Genome Activators, Developmental Timing, and Pluripotency.

The transcription factors Pou5f1, Sox2, and Nanog are central regulators of pluripotency in mammalian ES and iPS cells. In vertebrate embryos, Pou5f1/3, SoxB1, and Nanog control zygotic genome activation and participate in lineage decisions. We review the current knowledge of the roles of these genes in developing vertebrate embryos from fish to mammals and suggest a model for pluripotency gene regulatory network functions in early development.

Onichtchouk D ，Driever W 《-》

In vitro analysis of the transcriptional regulatory mechanism of zebrafish pou5f3.

Zebrafish pou5f3 (previously named pou2), a close homologue of mouse Oct4, encodes a PouV-family transcription factor. pou5f3 has been implicated in diverse aspects of developmental regulation during embryogenesis. In the present study, we addressed the molecular function of Pou5f3 as a transcriptional regulator and the mechanism by which pou5f3 expression is transcriptionally regulated. We examined the influence of effector genes on the expression of the luciferase gene under the control of the upstream 2.1-kb regulatory DNA of pou5f3 (Luc-2.2) in HEK293T and P19 cells. We first confirmed that Pou5f3 functions as a transcriptional activator both in cultured cells and embryos, which confirmed autoregulation of pou5f3 in embryos. It was further shown that Luc-2.2 was activated synergistically by pou5f3 and sox3, which is similar to the co-operative activity of Oct4 and Sox2 in mice, although synergy between pou5f3 and sox2 was less obvious in this zebrafish system. The effects of pou5f3 deletion constructs on the regulation of Luc-2.2 expression revealed different roles for the three subregions of the N-terminal region in Pou5f3 in terms of its regulatory functions and co-operativity with Sox3. Electrophoretic mobility shift assays confirmed that Pou5f3 and Sox3 proteins specifically bind to adjacent sites in the 2.1-kb DNA and that there is an interaction between the two proteins. The synergy with sox3 was unique to pou5f3-the other POU factor genes examined did not show such synergy in Luc-2.2 regulation. Finally, functional interaction was observed between pou5f3 and sox3 in embryos in terms of the regulation of dorsoventral patterning and convergent extension movement. These findings together demonstrate co-operative functions of pou5f3 and sox3, which are frequently coexpressed in early embryos, in the regulation of early development.

Kobayashi K ，Khan A ，Ikeda M ，Nakamoto A ，Maekawa M ，Yamasu K ... -  《-》

Sox2/Oct4: A delicately balanced partnership in pluripotent stem cells and embryogenesis.

Considerable progress has been made in understanding the roles of Sox2 and Oct4 in embryonic stem cells and mammalian embryogenesis. Specifically, significant progress has been made in answering three questions about the functions of Sox2 and Oct4, which are the focus of this review. 1) Are the first or second cell lineage decisions during embryogenesis controlled by Oct4 and/or Sox2? 2) Do the levels of Oct4 and Sox2 need to be maintained within narrow limits to promote normal development and to sustain the self-renewal of pluripotent stem cells? 3) Do Oct4 and Sox2 work closely together or is the primary role of Sox2 in pluripotent cells to ensure the expression of Oct4? Although significant progress has been made in answering these questions, additional studies are needed to resolve several important remaining issues. Nonetheless, the preponderance of the evidence suggests there is considerable crosstalk between Sox2 and Oct4, and further suggests Sox2 and Oct4 function as molecular rheostats and utilize negative feedback loops to carefully balance their expression and other critical genes during embryogenesis. This article is part of a Special Issue entitled: The Oct transcription factor family, edited by Dr. Dean Tantin.

Rizzino A ，Wuebben EL 《-》

Pou5f1/oct4 in pluripotency control: insights from zebrafish.

Gastrulation in vertebrates is a conserved process, which involves transition from cellular pluripotency to early precursors of ectoderm, mesoderm, and endoderm. Pluripotency control during this stage is far from being understood. Recent genetic and transcriptomic studies in zebrafish suggest that the core pluripotency transcription factors (TFs) Pou5f1 and TFs of the SoxB1 group are critically involved in large-scale temporal coordination of gene expression during gastrulation. A significant number of evolutionary conserved target genes of Pou5f1 in zebrafish are also involved in stem-cell circuit in mammalian ES cell cultures. Here, I will review the roles of Pou5f1 in development and discuss the evolutionary conservation of Pou5f1 functions and their relation to pluripotency control.

Onichtchouk D 《-》