Development of a multicellular organism uses the same genetic code to generate a broad diversity of cell types, which is instructed by extracellular cues and orchestrated by transcriptional activators and repressors. While transcription factors establish cell identities according to the central dogma, a number of enzymes, which index and regulate chromatin, appear to perform essential functions as well. We optimized a versatile experimental and analytical approach that allows for rapid perturbation of genes and the recovery of high replicate powered phenotypic information. We applied this set-up to investigate a panel of epigenetic regulators that are essential for early gestation. Our comparative analysis approach enabled us to pinpoint affected genetic pathways and cell lineage-specific effects that distinguish even closely related regulators, such as polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Moreover, by incorporating additional epigenetic data, we were able to identify early aberrations that partially explain how certain developmental abnormalities emerge at the onset of gastrulation. SOURCE: Helene Kretzmer (kretzmer@molgen.mpg.de) - Meissner Lab Max Planck Institute for Molecular Genetics

Pluto Bioinformatics

GSE137337: Epigenetic regulator function through mouse gastrulation