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Are TADs supercoiled?
Dusan Racko1,2,3, Fabrizio Benedetti1,4, Julien Dorier1,4
1Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Nucleic Acids Research
|November 6, 2018
Summary
Topologically associating domains (TADs) are key chromosomal structures. Transcription-induced supercoiling may explain how TADs form and facilitate enhancer-promoter interactions within these functional genomic regions.
Area of Science:
- Genomics
- Molecular Biology
- Chromatin Structure
Background:
- Topologically associating domains (TADs) are fundamental units of interphase chromosome organization in eukaryotes.
- TADs exhibit a higher frequency of intra-chromosomal interactions compared to inter-TAD interactions.
- Enhancer and promoter elements are typically confined within the same TAD, enabling long-range gene regulation.
Purpose of the Study:
- To investigate the mechanisms underlying TAD formation and internal structure.
- To explore the role of supercoiling in establishing TADs and facilitating enhancer-promoter communication.
Main Methods:
- Survey of experimental studies on supercoiling in interphase chromosomes.
- Review of numerical simulations modeling transcription-induced supercoiling in chromatin fibers.
Main Results:
- Supercoiling is experimentally observed in interphase chromosomes.
- Simulations suggest transcription-induced supercoiling can form TADs.
- This mechanism potentially explains efficient enhancer-promoter interactions within TADs.
Conclusions:
- Transcription-induced supercoiling is a plausible mechanism for TAD formation.
- Supercoiling may explain the functional compartmentalization of chromosomes into TADs.
- This sheds light on the principles of 3D genome organization and gene regulation.
