Timing of cell fate decisions by stem cell transcription factors

Dr. Daria Onichtchouk (Institute of Biology I, University of Freiburg)

Every vertebrate organism, developing from the zygote, passes through zygotic gene activation point, called midblastula transition (MBT), when the set of zygotic genes starts to be transcribed in a rapid and timely coordinated manner. We have shown, that in zebrafish embryos Pou5f1 and SoxB1 transcription factors bind to regulatory regions of hundreds of early zygotic genes, and activate them at MBT. Pou5f1-SoxB1 binding sites are enriched in various chromatin modifications and RNA polymerase II at MBT and shortly before. The question, how epigenetic chromatin modifiers are recruited to DNA to regulate gene expression, is not entirely clear in any of the vertebrate model systems, and is of great biological and medical importance. In this project we will use mutant analysis and time resolution of developing embryos, to address causal relationships between Pou5f1 and SoxB1 binding, positioning of the epigenetic marks, and expression of the target genes at the earliest stages of zebrafish embryogenesis.

Sketches of zebrafish embryos at 2,5 and 3 hours of development from Kimmel et al., 1995, Dev. Dyn. 203)