Researchers Reveal the Pioneering Role of Zelda in Zygotic Gene Activation

Photo of Melissa HarrisonResearchers at the University of Wisconsin School of Medicine and Public Health have developed a novel strategy to address the role of vital proteins during early embryonic development.

In all animals, early development is controlled by products put into the egg by the mother, and it is not until hours or days later that the zygote takes control of its own development. During this time, the genome of the zygote remains silent as it is reprogrammed to allow for the development of an entirely new organism.

Specialized proteins, termed pioneer transcription factors, drive this reprogramming both in the early embryo and in laboratory cultures during the generation of induced pluripotent stem cells (iPSC). While this pioneer factor-mediated reprogramming is essential for development, much remains unknown about how these proteins function, according to Melissa Harrison, associate professor of biomolecular chemistry.

Using fruit flies to model this conserved process, Harrison’s team uncovered fundamental features of the protein, Zinc finger early Drosophila activator protein, or Zelda, which is a pioneer transcription factor necessary for preparing the early embryo for development.

“We set out to test whether this essential protein was continuously required to reprogram the genome or whether it was only required during the initial phases and that the process was then carried out by additional, downstream factors,” Harrison said.

The research was recently published in the journal Molecular Cell.

A major challenge, however, was the rapid nature of this early development.

To overcome this challenge, the researchers developed a strategy that uses blue light to rapidly and reversibly inactivate Zelda – a literal light switch to turn “off” or turn “on” Zelda function. Using this novel technique, they showed that Zelda was required throughout the process of genomic reprogramming.

Read more about this work at the link below.