Genome organization controls transcriptional dynamics during development.

TitleGenome organization controls transcriptional dynamics during development.
Publication TypeJournal Article
Year of Publication2022
AuthorsBatut, PJ, Bing, XYang, Sisco, Z, Raimundo, J, Levo, M, Levine, MS
JournalScience
Volume375
Issue6580
Pagination566-570
Date Published2022 02 04
ISSN1095-9203
KeywordsAnimals, Chromatin, Chromosomes, Insect, Drosophila, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Genes, Homeobox, Genes, Insect, Genome, Insect, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Single-Cell Analysis, Transcription, Genetic
Abstract

<p>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 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.</p>

DOI10.1126/science.abi7178
Alternate JournalScience
PubMed ID35113722
Grant ListR35 GM118147 / GM / NIGMS NIH HHS / United States