Eukaryotic chromosomes are organized in multiple scales, from nucleosomes to chromosome territories. Recently, genome-wide methods identified an intermediate level of chromosome organization, topologically associating domains (TADs), that play key roles in transcriptional regulation. However, these methods cannot directly examine the interplay between transcriptional activation and chromosome organization while maintaining spatiotemporal information. Here, we present a multiplexed, sequential imaging approach (Hi-M) that permits the simultaneous detection of chromosome organization and transcription in single nuclei. We used Hi-M to study chromosome organization during the awakening of the zygotic genome in intact Drosophila embryos. By visualizing chromosome architecture and gene expression simultaneously in single nuclei, we were able to unveil the changes in 3D chromatin organization occurring upon transcriptional activation and homologous chromosome un-pairing. Excitingly, the ability of Hi-M to explore the multi-scale chromosome architecture in time and space will be key to understand the mechanisms and consequences of the 4D organization of the genome.
Cardozo Gizzi, Andrés M. and Cattoni, Diego I. and Fiche, Jean-Bernard and Espinola, Sergio M. and Gurgo, Julian and Messina, Olivier and Houbron, Christophe and Ogiyama, Yuki and Papadopoulos, Giorgio-Lucio and Cavalli, Giacomo and Lagha, Mounia and Nollmann, Marcelo, Microscopy-Based Chromosome Conformation Capture Enables Simultaneous Visualization of Genome Organization and Transcription in Intact Organisms (October 13, 2018). Available at SSRN: https://ssrn.com/abstract=3265728 or http://dx.doi.org/10.2139/ssrn.3265728
This version of the paper has not been formally peer reviewed.
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