Microscopy-based chromosome conformation capture enables simultaneous visualization of genome organization and transcription in intact organisms

CATTONI, DIEGO I.; CARDOZO GIZZI, ANDRES M.; FICHE, JEAN-BERNARD; ESPINOLA, SERGIO M.; GURGO, JULIAN; MESSINA, OLIVIER; HOUBRON, CHRISTOPHE; OGIYAMA, YUKI; PAPADOPOULOS, GIORGIO L.; CAVALLI, GIACOMO; LAGHA, MOUNIA; NOLLMANN, MARCELO

Banff

Simposio; Keystone Symposia-3D Genome: Gene Regulation and Disease; 2019

Keystone Symposia

Eukaryotic chromosomes are organized in multiple scales, from nucleosomes tochromosome territories. Recently, genome-wide methods identified an intermediate level ofchromosome organization, topologically associating domains (TADs), that play key roles intranscriptional regulation. However, these methods cannot directly examine the interplaybetween transcriptional activation and chromosome architecture while maintaining spatialinformation. Here, we present a multiplexed, sequential imaging approach (Hi-M) thatpermits the simultaneous detection of chromosome organization and transcription in singlenuclei. This allowed us to unveil the changes in 3D chromatin organization occurring upontranscriptional activation and homologous chromosome un-pairing during the awakening ofthe zygotic genome in intact Drosophila embryos. Excitingly, the ability of Hi-M to explore themulti-scale chromosome architecture with spatial resolution at different stages ofdevelopment or during the cell cycle will be key to understand the mechanisms andconsequences of the temporal and spatial organization of the genome.