A model of CTCF-mediated loop establishment during medaka development. At the morula stage, loops and contact domains do not exist, but CTCF is already bound to the future loop anchors. At the blastula stage, zygotic genome activation occurs, and small contact domains start to emerge by loop extrusion of cohesin. The boundaries of large contact domains are also detectable at this stage, but stable loops are not formed. During gastrulation, large contact domains and stable loops emerge, and this could be explained by an increase in the processivity of cohesin or the strength of CTCF-cohesin binding, or prolonged cell cycle length.
