University of Massachusetts Medical School Faculty Publications
UMMS Affiliation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Publication Date
2017-01-09
Document Type
Article Preprint
Disciplines
Computational Biology | Genetic Phenomena | Genomics | Molecular Biology | Structural Biology
Abstract
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and segmental organization into topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding, and CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data supports that CTCF mediates transcriptional insulator function through enhancer-blocking but not direct chromatin barrier activity. These results define the functions of CTCF in chromosome folding, and provide new fundamental insights into the rules governing mammalian genome organization.
Keywords
genomics, chromosome folding, CTCF, topologically associating domains, TADs
Rights and Permissions
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/095802
Source
bioRxiv 095802; doi: https://doi.org/10.1101/095802. Link to preprint on bioRxiv service.
Journal/Book/Conference Title
bioRxiv
Repository Citation
Nora, Elphege P.; Goloborodko, Anton; Valton, Anne-Laure; Gibcus, Johan H.; Uebersohn, Alec; Abdennur, Nezar; Dekker, Job; Mirny, Leonid A.; and Bruneau, Benoit, "Targeted degradation of CTCF decouples local insulation of chromosome domains from higher-order genomic compartmentalization" (2017). University of Massachusetts Medical School Faculty Publications. 1566.
https://escholarship.umassmed.edu/faculty_pubs/1566
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Computational Biology Commons, Genetic Phenomena Commons, Genomics Commons, Molecular Biology Commons, Structural Biology Commons