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University of Massachusetts Medical School Faculty Publications

2017

Chromosome folding

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Full-Text Articles in Molecular Biology

Targeted Degradation Of Ctcf Decouples Local Insulation Of Chromosome Domains From Higher-Order Genomic Compartmentalization, Elphege P. Nora, Anton Goloborodko, Anne-Laure Valton, Johan H. Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A. Mirny, Benoit Bruneau Jan 2017

Targeted Degradation Of Ctcf Decouples Local Insulation Of Chromosome Domains From Higher-Order Genomic Compartmentalization, Elphege P. Nora, Anton Goloborodko, Anne-Laure Valton, Johan H. Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A. Mirny, Benoit Bruneau

University of Massachusetts Medical School Faculty Publications

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 ...