How our genes are read at the beginning of life
Researchers from the Institute for Epigenetics and Stem Cells at Helmholtz Munich studied RNA Polymerase II (Pol II) in early mouse embryos and shed light on transcriptional elongation during zygotic genome activation (ZGA), a key process of development where the control of gene expression passes on from the mother to the embryo. Their findings are published in Cell Reports.
How transcription is regulated within hours after fertilization of the egg by the sperm can tells us about how embryonic development comes under the exclusive control of the embryonic genome rather than the maternal genome.
In a recent study, the researchers Kenichiro Abe, Tamas Schauer, and Maria-Elena Torres-Padilla established a modified version of ChIL-seq (Chromatin Integration Labeling) to study the distribution of phosphorylated RNA polymerase II during ZGA in mouse embryos. In differentiated cells, the main phosphorylated forms of the RNA Polymerase II demarcate ‘initiation’ or ‘elongation’ of transcription. In other words, how the RNA Polymerase II starts to read our genes versus how it generates messenger mRNA from them. Abe, Schauer et al. now report that in embryos, the distribution patterns of the two phosphorylation forms of RNA Polymerase II are rather indistinguishable from each other during ZGA and that their distinctive pattern only emerges after ZGA.
Most excitingly, the authors identify factors, which regulate transcriptional elongation in early embryos. The authors find that some of these factors can also prevent the activation of genes at the wrong developmental stage. “By generating genome-wide maps of the RNA Polymerase II in early embryos and identifying genes regulated by the factors that the RNA Polymerase associates with, we now understand better how this key process is regulated during the very early stages of life.” Says Maria-Elena, the corresponding author of the work.
This work builds up on research of the Torres-Padilla lab that aims to understand how the very early cells in the embryo, which are totipotent and thus can generate all cells in the body, read, write and interpret their genome.
Abe et al. (2022). Distinct patterns of RNA Polymerase II and transcriptional elongation characterize mammalian genome activation. Cell Reports