Our Latest Research

Genome organization controls transcriptional dynamics and supports coupling of distant regulatory genes during development

Past studies offer contradictory claims for the role of genome organization in the regulation of gene activity. Here, we show through high-resolution chromosome conformation analysis that the Drosophila genome is organized by two independent classes of regulatory sequences, tethering elements and insulators. Quantitative live imaging and targeted genome editing demonstrate that this tethering element dependent genome organization is critical for the precise temporal dynamics of gene transcription and co-dependent transcriptional dynamics of genes separated by large genomic distances in living Drosophila embryos. Tethering elements mediate long-range enhancer-promoter interactions and foster fast activation kinetics and provide extensive physical and functional associations of distant paralogous genes, including co-regulation by shared enhancers and co-transcriptional initiation over distances of nearly 250 kilobases. 

Philippe J. Batut et al. Science 2022, and Michal Levo, João Raimundo, et al. Nature 2022.

Comprehensive single-cell transcriptome lineages of a proto-vertebrate

Ascidian embryos highlight the importance of cell lineages in animal development. As simple proto-vertebrates, they also provide insights into the evolutionary origins of cell types such as cranial placodes and neural crest cells. Here we have determined single-cell transcriptomes for more than 90,000 cells that span the entirety of development—from the onset of gastrulation to swimming tadpoles—in Ciona intestinalis. Owing to the small numbers of cells in ascidian embryos, this represents an average of over 12-fold coverage for every cell at every stage of development. We used single-cell transcriptome trajectories to construct virtual cell-lineage maps and provisional gene networks for 41 neural subtypes that comprise the larval nervous system. We summarize several applications of these datasets, including annotating the synaptome of swimming tadpoles and tracing the evolutionary origin of cell types such as the vertebrate telencephalon.

Cao Chen, Lemaire A. Laurencehref, et al. Nature 2019.

Related People

Tyler Heist
QCB Graduate Alumni
Mike Levine
Anthony B. Evnin '62 Professor in Genomics, Professor of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics
Prakriti Paul
QCB Graduate Alumni