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

Abstract

Resolution and formation of facultative heterochromatin is essential to development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood due to the inability to study 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, indicating that changes in DNA topology through (de-)catenation rather than release of torsional stress through swiveling is necessary for heterochromatin resolution. In turn, TOP2 and BAF cooperate to recruit pluripotency factors, explaining some of the instructive roles of BAF complexes. Unexpectedly, we found that TOP2, also plays a role in the reformation of facultative heterochromatin, suggesting that facultative heterochromatin and accessible chromatin exist at different states of catenation or other topologies, which may be critical to their structures.