Genome organization controls transcriptional dynamics during development.

Tytuł:: Genome organization controls transcriptional dynamics during development.
Autorzy:: Batut PJ; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Bing XY; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Sisco Z; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Raimundo J; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Levo M; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Levine MS; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
Źródło:: Science (New York, N.Y.) [Science] 2022 Feb 04; Vol. 375 (6580), pp. 566-570. Date of Electronic Publication: 2022 Feb 03.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural
Język:: English
Imprint Name(s):: Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
MeSH Terms:: Gene Expression Regulation, Developmental*
Genes, Homeobox*
Genome, Insect*
Transcription, Genetic*
Drosophila/*genetics
Animals ; Chromatin/chemistry ; Chromatin/genetics ; Chromosomes, Insect/chemistry ; Chromosomes, Insect/genetics ; Drosophila/embryology ; Enhancer Elements, Genetic ; Genes, Insect ; Promoter Regions, Genetic ; Regulatory Sequences, Nucleic Acid ; Single-Cell Analysis
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Grant Information:: R35 GM118147 United States GM NIGMS NIH HHS
Substance Nomenclature:: 0 (Chromatin)
Entry Date(s):: Date Created: 20220203 Date Completed: 20220211 Latest Revision: 20230726
Update Code:: 20240104
PubMed Central ID:: PMC10368186
DOI:: 10.1126/science.abi7178
PMID:: 35113722
: Czasopismo naukowe

Pełny tekst

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.

Comment in: Science. 2022 Feb 4;375(6580):491-492. (PMID: 35113712)

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