Lightsheet Micrograph of Zebrafish Embryo.

eLife paper on ZGA timing: activator-repressor competition

Our study demonstrating how repressors (histones) and activators (transcription factors) jointly control transcription in the zebrafish embryo is now available online: Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos. Joseph et al. eLife (2016)

Competition Model

In this study, lead by Shai Joseph (Vastenhouw Lab) and carried out collaboratively with the Shevchenko and Zaburdaev lab, we could quantitatively address a long-standing question: how is the timing at which transcription starts in embryos controlled?

By a combination of quantitative, molecular, and functional techniques, we found that the two most prominent hypotheses, the "depleted repressor" and the "increasing activator" models, can be unified in a competition model. Here, repressing histones and activating transcription factors go head-to-head competing for access to DNA target sites.

Additionally, the nuclear-to-cytoplasmic ratio - often defined in the number of genomes in an embryo - resurfaced as a key concept, though in the form of a volume ratio between cell nuclei and overall cytoplasm. While the global concentration of not DNA-bound histones did not change at the time of transcription onset, we detected a marked decrease in the concentration of not DNA-bound histones specifically within cell nuclei.