During animal embryogenesis, complex changes in gene expression patterns drive body morphogenesis. Nuclear organisation is a key factor in gene regulation, by controlling transcription factor (TF) interactions and gene accessibility through histone modifications and genome topology, but to what extent does nuclear organisation vary at the single-cell level? To tackle this question, Albert Tsai and Justin Crocker use immunofluorescent imaging of TFs and histones in developing Drosophila embryos. The authors show that the TFs Hunchback and Krüppel initially have a uniform distribution but form distinct nuclear regions as development proceeds. TFs that are expressed later (Ultrabithorax and Engrailed) are spatially defined when first transcribed, indicative of TF distribution being defined by the nuclear architecture at the point at which they are expressed. Histone modifications become more spatially heterogeneous during development, and modifications at the hunchback transcription start site have a distinct ‘signature’ when compared with the global distribution. In addition, histone modifications associated with a single gene can vary depending on the spatial location of the cell (e.g. proximity to transcriptional repressors) and the time of gene expression. Together, these data reveal complex nuclear rearrangements that are crucial for gene regulation occur during embryogenesis.
