New insight into the chromosome-level regulation of gene expression

© 2023 EPFL

© 2023 EPFL

The Bioinformatics Competence Center (BICC) participated in the discovery of a new regulatory mechanism involved in gene expression control in the Drosophila nervous system.

The BICC contributed to a study led by the Gambetta lab (CIG, UNIL) reporting the discovery of “meta-domains” - a previously unreported level of genome folding whereby distant pairs of Topologically Associating Domains (TADs) that are megabases apart come together in specific pairs. This study demonstrates that within meta-domains, “meta-loops” tether neuronal gene promoters involved in axon guidance and signaling and structural intergenic elements. Meta-loops critically enable neuronal gene activation in mature Drosophila neurons. Meta-loops are formed by dedicated transcription factors and represent the longest-range regulatory associations reported to date in any genome. The BICC scientists involved in this study deployed their expertise in three-dimensional (3D) genome organization and single-cell analyses to comprehensively describe this novel paradigm of genome folding in the developing fly nervous system.

References

Mohana G, Dorier J, Li X, Mouginot M, Smith RC, Malek H, Leleu M, Rodriguez D, Khadka J, Rosa P, Cousin P, Iseli C, Restrepo S, Guex N, McCabe BD, Jankowski A, Levine MS, Gambetta MC. Chromosome-level organization of the regulatory genome in the Drosophila nervous system. Cell. 2023 Jul 25;S0092-8674(23)00741-9. doi:10.1016/j.cell.2023.07.008.