Genome organization controls transcriptional dynamics during development

Philippe J. Batut, Xin Yang Bing, Zachary Sisco, João Raimundo, Michal Levo, Michael S. Levine

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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 two-tiered organization is critical for the precise temporal dynamics of Hox gene transcription during development. Tethering elements mediate long-range enhancer-promoter interactions and foster fast activation kinetics. Conversely, the boundaries of topologically associating domains (TADs) prevent spurious interactions with enhancers and silencers located in neighboring TADs. These two levels of genome organization operate independently of one another to ensure precision of transcriptional dynamics and the reliability of complex patterning processes.

Original languageEnglish (US)
Article numberA36
Issue number6580
StatePublished - Feb 4 2022

All Science Journal Classification (ASJC) codes

  • General


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