Low-input genomics screening reveals epigenetic pathways that orchestrate nuclear organization in early mouse embryos.

The three-dimensional folding of the genome within the nuclear space is fundamental for regulating various DNA-related processes. How nuclear organization is first established during development is not understood at the molecular level. The formation of lamina-associated domains (LADs) at the nuclear periphery represents the earliest feature of nuclear organization. In this study, we conducted a screening to investigate the molecular mechanisms regulating LAD establishment in vivo, using mouse embryos. Our findings identify histone methylation pathways that cause severe disruption of nuclear architecture in early embryos. This research provides an unprecedented resource for understanding the molecular basis of nuclear organization establishment highlighting the hierarchical relationships between chromatin pathways during epigenome formation and allows for interrogation of its impact at the onset of mammalian development. This SuperSeries is composed of the SubSeries listed below.