The Trithorax group protein dMLL3/4 instructs the assembly of the zygotic genome at fertilization

Global context and preprint summary

Oocyte-to-embryo (O-to-E) transition requires the assembly of two completely differently configured haploid genomes. For the pronuclei to merge into a single zygotic genome after fertilization, the parental chromatin needs to be extensively remodeled. A previous study has shown that the Trithorax-group chromatin remodeling proteins MLL3 and MLL4 are essential for the zygote to reprogram to pluripotency, but are dispensable for the maintenance of cell identity. In the current work, the authors find that the Drosophila dMLL3/4 proteins play a role in O-to-E transition through their chromatin remodeling and/or gene regulatory capacities. They identify a novel gene, IDGF4, which is required for O-to-E and is under the transcriptional control of dMLL3/4.

My favorite experiment in this study:

Although it is known that MLL3/4 was needed to establish the pluripotent cell state, the timing of this requirement has been unclear. To test this, the authors depleted these proteins specifically in the fly germline, and counted egg-hatching events after fertilization. Eggs from dMLL3/4 depleted females did not hatch due to a failure to enter embryogenesis at the first mitotic division, whereas depletion of these proteins in males did not affect the embryogenesis process. I think this experiment is great because it shows conclusively that maternally-provided dMLL3/4 is necessary before O-to-E can occur upon fertilization.

What I like about this work:

Despite our relatively broad knowledge on embryogenesis, still many aspects of this intriguing process remain elusive. This study from Prudêncio et al. strengthens the emerging concept that chromatin remodeling factors are important to reshape the genomic and transcriptomic landscapes in each of the embryogenesis stages independently. I like this study because it does not only pinpoint the exact timing of a known phenotype, but it also provides the first mechanistic insights into its establishment through the identification of a maternally encoded factor acting on the paternal genome.

Figure

The figure shows the model proposed by the authors of how the dMLL3/4-dependent gene expression signature might be necessary for the cell to undergo oocyte-to-embryo transition and accomplish the assembly of the zygotic genome.
(From preprint, made available under a CC-BY-NC-ND 4.0 International license).

Tags: dmll3/4, drosophila, maternal effect genes, oocyte-to-embryo transition

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