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Nat Struct Mol Biol. 2017 Apr;24(4):344-352. doi: 10.1038/nsmb.3384. Epub 2017 Feb 27.

TOP2 synergizes with BAF chromatin remodeling for both resolution and formation of facultative heterochromatin.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
2
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA.
3
Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
4
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
5
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
6
Harvard Society of Fellows, Harvard University, Cambridge, Massachusetts, USA.
7
Systems Biology Center, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA.
8
Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.

Abstract

The resolution and formation of facultative heterochromatin are essential for development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood owing to the difficulty of studying heterochromatin dynamics and structure in vivo. We devised an in vivo approach to investigate these mechanisms and found that topoisomerase II (TOP2), but not TOP1, synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin independent of transcription. This indicates that changes in DNA topology that take place through (de-)catenation rather than the release of torsional stress through swiveling are necessary for heterochromatin resolution. TOP2 and BAF cooperate to recruit pluripotency factors, which explains some of the instructive roles of BAF complexes. Unexpectedly, we found that TOP2 also plays a role in the re-formation of facultative heterochromatin; this finding suggests that facultative heterochromatin and accessible chromatin exist at different states of catenation or other topologies, which might be critical to their structures.

PMID:
28250416
PMCID:
PMC5395302
DOI:
10.1038/nsmb.3384
[Indexed for MEDLINE]
Free PMC Article

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