Presenter: Christine A. Rushlow, PhD (NYU)
Topic: An “individualist” model of an active genome in a developing embryo
The early Drosophila embryo provides unique experimental advantages for addressing fundamental questions of gene regulation at multiple levels of organization, from individual gene loci to the entire genome. Using 1.5-hour old Drosophila embryos undergoing the first wave of genome activation1, we detected ~110 discrete “speckles” of RNA Polymerase II (Pol-II) per nucleus, two of which were larger and localized to the histone locus bodies (HLBs)2,3. In the absence of the primary driver of Drosophila genome activation, the pioneer factor Zelda (Zld)1,4,5, 70% fewer speckles were present, however, the HLBs tended to be larger than wild-type (wt) HLBs, indicating that Pol-II accumulates at the HLBs in the absence of robust early-gene transcription. We observed a uniform distribution of distances between active genes in the nuclei of both wt and zld mutant embryos, indicating that early co-regulated genes do not cluster into nuclear sub-domains. However, in instances whereby transcribing genes did come into close 3D proximity (within 400 nm), they were found to have distinct Pol-II speckles. In contrast to the emerging model whereby active genes are clustered to facilitate co-regulation and sharing of transcriptional resources, our data support an “individualist” model of gene control at early genome activation in Drosophila. This model is in contrast to a “collectivist” model where active genes are spatially clustered and share transcriptional resources, motivating rigorous tests of both models in other experimental systems.